It has an effect on many body systems, underscoring its importance for men's physical health and fertility. The development and maintenance of muscular mass, bone density, and general physical strength depend heavily on testosterone, a hormone that plays a complicated and significant role in men's physiology. All data analyzed during this study are included in this published article or in the data listed in “References.” As a result, their dosing is not very flexible and does not permit easy titration, which is essential for therapy in adolescents. Since available findings are contradictory, it is precarious to draw a conclusion as to the effects of pravastatin on male reproductive function, especially from a human studies’ perspective. Nevertheless, further studies are needed to establish a baseline understanding of the effects of fluvastatin on male reproductive parameters; whether it affects male fertility remains debatable. Therefore, this review aimed to analyze the current literature regarding the effect of statin treatment on male reproductive and sexual health. Fats, carbohydrates, and proteins affect sperm quality by acting on oxidative stress and testosterone levels, whose common target are the mitochondria. While an excess of simple carbohydrates negatively affects sperm function, there are no studies about the role of complex carbohydrates on male reproductive potential. Naturally existing testosterone is no doubt important when it comes to a man’s levels of fertility. While testosterone therapy can be effective for certain purposes, the treatment does not come without risks. Certain testosterone supplements are available over-the-counter that help boost natural testosterone levels. Masculinizing hormone therapy is preferably started during puberty to suppress secondary sexual characteristic developments, such as menstruation and growth of the breasts. A relatively modern reason for testosterone therapy is masculinization, or female-to-male transitioning in order to match gender identity. A recent randomized controlled trial conducted in Malaysia investigated the efficacy and safety of TU in the treatment of aging men with TD Tan et al. 2013. Collectively in these trials, only one case of prostate cancer was observed during the study periods in over 2000 men. A prospective trial followed 81 men (mean age 57 years) for a mean (range) of 33.8 (6–144) months after starting TRT Coward et al. 2008. While the primary outcomes of the study focused on the metabolic syndrome, secondary outcomes included various prostate parameters. A retrospective study reviewed Surveillance, Epidemiology, and End Results Medicare data on nearly 150,000 men over a 15-year period and compared prostate cancer outcomes in men who had received TRT prior to prostate cancer diagnosis and those who did not Kaplan and Hu, 2013. Steroids can have long-term impacts on overall male health The primary objective of this systematic review is to critically analyze the chosen articles and provide a clear understanding of the current knowledge regarding the association between testosterone and vitamin D levels. Both animal and human studies present conflicting data on whether statins do, in fact, influence fertility outcomes. Future investigation should now include whether the testis, the blood-testis-barrier, the Sertoli cells, and even the Leydig cells and other spermatogenic cells have these transporters and whether their function is the same in these cells. Conversely, one study showed the dose-dependent antioxidant and anti-apoptotic properties of rosuvastatin on diabetes-induced reproductive damage . Sartorius et al. showed, that there was no decline in testosterone levels in males who self-reported to be in very good health. Oleuropein supplementation increases urinary noradrenaline and testicular testosterone levels and decreases plasma corticosterone level in rats fed high-protein diet. Low endogenous T levels correlate with an increased risk of adverse CVD events, and endothelial dysfunction and increased atherosclerosis are means by which male hypogonadism may contribute to an increased risk of death Jackson et al. 2010. And when it comes to recreational drugs, their overall impact on your physical and mental well-being can be far-reaching, which puts your health at risk in a number of ways. Urologist Sarah Vij, MD, walks you through some of the most common substances — from antidepressants to opioids — that can affect fertility in men. If you’re dreaming of becoming a parent, it’s important to know that certain drugs, both legal and illegal, can have a negative effect on your fertility. These are hypotheses, but in addition, another important risk factor is the genetic predisposition to develop SRM, as these symptoms are not always observed in all patients. Nevertheless, mechanisms that involve the disruption of the supply of farnesyl and geranyl pyrophosphate, or via mitochondrial dysfunction and calcium ion leakage have been implicated. SRM is characterized by generalized muscular pain in addition to muscular weakness, stiffness, and cramps in the thighs and calves attributable to the increase in creatine kinase concentration, myositis, rhabdomyolysis, tendinitis, and myalgia. Statin-related myotoxicity (SRM) is a common adverse event of statin usage that occurs within the first year of treatment commonly due to either the nocebo and/or actual effect, resulting in varying degrees of exertional fatigue, disorientation, and amnesia. However, they are all based on expert opinion or consensus rather than evidence provided by carefully designed studies 10, 22, 37, 62.Though the dynamics of Zn during sperm expansion is far to be ambiguous but, the significant role of Zn in normal spermatogenesis and sperm suitability is known.While such phenomena are not experienced by every patient, exogenous testosterone can lead to the atrophy of the germinal epithelium in normal men and suppresses spermatogenesis, leading to azoospermia after 10 weeks of use.9 Testicular atrophy is not uncommon, and it usually is reflective of loss of both spermatogenesis and Leydig cell function.In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population.For example, if there is low testosterone during puberty, a boy may not develop facial hair or experience the same level of penile or bodily growth.We used pyrolysis gas chromatography-mass spectrometry (Py-GC-MS) for PS-MPs detection in testicular tissue due to their ability to detect MPs of any size without prior separation41.Within the seminiferous tubules, only Sertoli cells possess receptors for both FSH and testosterone. Considering popping testosterone supplements and wondering, “can testosterone increase penis size? Furthermore, it is crucial for subsequent studies to explore the efficacy of various GLP-1 RAs in the treatment of MFI, as the current literature has not yet explored this. Monitoring the hormonal profile of the HPG axis, along with repeated semen analyses including in-depth assessments of sperm quality, such as sperm DNA integrity and epigenetics, is necessary. In conclusion, current evidence suggests that using GLP-1RA in preconception treatment may offer new approaches for managing weight and infertility in men with obesity. Testosterone is used as treatment for males with late onset hypogonadism, a condition in men who experience symptoms caused by a decrease in serum testosterone. The purpose of this review is to discuss the contraceptive properties of testosterone therapy and to discuss strategies to increase testosterone in men with the desire to preserve fertility. Despite its positive effects on sexual function, it has a negative effect on fertility. The hormone levels were shown to be altered by high cholesterol levels, and thus, exposure to fluvastatin helped to restore normal FSH, LH, and testosterone levels. The researchers found that exposure to fluvastatin prevented testicular atrophy, promoted sperm quality, and increased the number of spermatogonia, Leydig, and Sertoli cells. The tests included the testicular weight and gross morphology, sperm parameters, circulating sex hormones, lipid levels, and the tissue mammalian target of rapamycin (mTOR)/Ribosomal protein S6 kinase beta-1 (p70s6k). In fact, a similar study of comparable size and design did not observe such an increase in CVD events among men randomized to the T arm . In aggregate, though there have been mixed results regarding the relationship between low endogenous T levels and incident CVD, these studies suggest that, if anything, higher T levels may be protective. T levels were then measured in stored blood samples from initial study visits and analyzed for differences between the two groups. An alternative approach, employed to examine the association between T levels over time and CVD, was a nested case–control study within the Baltimore Longitudinal Study of Aging and the Multiple Risk Factors Intervention Trial . Additional longitudinal studies have similarly found that neither high nor low T levels predict incident myocardial infarction 14–16. In addition, health care providers also need to be educated about side effects of AAS and precise diagnostic testing. HCG is known to preserve testicular function and prevent testicular atrophy. For patients with histopathological abnormalities (namely, sperm maturation arrest), IVF-ICSI has been used but there is no published data confirming the success. Conservative or medical management forms the initial protocol for the management of AAS-induced male infertility. It is, thus, clear that small studies can only describe a very small window of the whole complex physiology. Many variables add to the complex interactions between testosterone and the brain. Most of the published literature agrees on the fact that testosterone is anxiolytic, anti-depressant and improves spatial abilities. An alternative is to analyze the behavior rapidly after testosterone injection, as it take roughly 30 min to induce gene expression changes. Another experiment on intact rats revealed that the effect of testosterone on depression is dose-dependent (Buddenberg et al., 2009). The biology of the association between testosterone and depression has been reviewed recently (Mchenry et al., 2014). The meta-analyses of the published studies are also to be taken into account. On the other hand, in both men and women, testosterone supplementation leads to improvement of depressive symptoms (Pope et al., 2003; Miller et al., 2009). This suggests that the causality could be different than predicted—depression lowers testosterone. Defects in Leydig cell mitochondria are responsible for oxidative damages in lipids, proteins, and mitochondrial DNA (mtDNA) and cause a decrease in ATP levels and an increase in ROS production . Excess fat tissue results in the increased activity of aromatase, which is an enzyme responsible for converting testosterone to estradiol . According to this hypothesis, diabetic male rats showed a decrease in sperm motility 34,35, which was restored after insulin administration . Even later, the non-genomic effects are active in parallel with the gene expression changes. While within 30 min after administration, non-genomic effects are important, later genomic effects are expected to be the major mediator. But beyond cyclic variations, testosterone undergoes chaotic temporary changes that are usually described as noise. Among legumes, soy, in contrast to the other legumes, may have deleterious effects on spermatogenesis, even if the results are not concordant across the studies. In fact, homocysteine, functioning as a strong oxidative stress factor, can increase the reactive oxygen species which in turn can compromise the concentration of spermatozoa and their mobility. Some human studies have shown the protective effect of the consumption of dried fruit, in particular walnuts, date palm, hazelnut, and chestnut on male fertility 12, 51, 52. In this regard, some studies have highlighted the protective role of some fruit juices and extracts on male fertility. Ma et al. similarly showed that obese males had a reduction in sperm quality, including semen volume, sperm number, and total motile sperm count , but these findings are inconsistent across studies 8,15,16. However, the direct impact of GLP-1 RAs on male reproductive hormones remains unclear, necessitating further research to confirm their potential role in treating male infertility. Recent studies show that the use of GLP-1 RAs in obese males may enhance sperm metabolism, motility, and insulin secretion in vitro, along with positive effects on the human Sertoli cells. This study must be powered for CVD outcomes and, ideally, should examine TRT among a broad spectrum of hypogonadal men to stratify treatment effects by age and baseline health status, among other clinical variables. Nonetheless, controversy remains regarding treatment of male hypogonadism, in part due to a lack of clear understanding of the risk/benefit profile of therapy. For the Randomized Clinical Trials, the Cochrane Collaboration’s Tool (15) was used, for the Prospective Cohorts the Newcastle-Ottawa Scale (NOS) (16) and for the Cross-sectional Studies the AXIS tool (Assess the Quality of Cross-sectional studies) (17). To assess the risk assessment of each study, a different questionnaire was used depending on each study design. Strategy performed based on PICO acronym (patient, intervention, comparison, and outcome) and study objective using MESH terms. Among them are randomized clinical trial (RCT), prospective cohort (PC), cross-sectional study or ecological study (CSS). The authors concluded that overall, and particularly in trials not funded by the pharmaceutical industry, exogenous T increased the risk of cardiovascular-related events Xu et al. 2013. Two meta-analyses found no differences in cardiovascular events between TRT and placebo groups Fernandez-Balsells et al. 2010; Calof et al. 2005, while a more recent meta-analysis found that TRT increased the risk of cardiovascular events, although the data seemed to vary by source of research trial funding. Abstracts and book chapters were excluded from the search, yet relevant case studies were included in the search given the specificity and nature of the search topics. TD has been identified concomitantly with many comorbid health conditions in men, including cardiovascular disease (CVD), metabolic syndrome, diabetes mellitus, hypertension, and dyslipidemia, while positing an associative relationship. Can testosterone supplements affect male fertility – Dr. Vasan S S Currently, there are a variety of widely available T formulations, including topical gels and patches, intramuscular injections, subcutaneous pellets, and oral/buccal formulations that provide clinicians and male patients the opportunity to personalize replacement therapy. The estimated likelihood of adverse effects of long-term TRT is still essentially unknown, as overall high-quality evidence based upon prospective randomized trials to recommend for or against its use in most men with testosterone deficiency (TD) is lacking. The male reproductive system makes, stores and moves sperm. Testosterone replacement therapy can treat some types of male hypogonadism. Blood and semen parameters (morphology and motility) were measured before and during treatment, as well as for three months after treatment. In contrast, a study demonstrated the benefits of atorvastatin as a protective drug against busulfan-induced spermatogenesis injury in Wistar rats. Following treatment, findings showed a decrease in the number of Sertoli cells, spermatogonia, and spermatocytes when compared to the control group . The LDL receptor transportation is also activated, leading to the increase of LDL receptors which amplifies LDL-C uptake and reduces the plasma LDL-C levels . Another cross-sectional study conducted by Chin Kok Yong et al. on 382 Malaysian men provided further insights. Further research with larger sample sizes would be beneficial to corroborate these findings and enhance our understanding of the complex relationship between vitamin D and hormone regulation. Moreover, the prevalence of contemporary lifestyles characterized by limited sunlight exposure and dietary diversity has significantly contributed to the pervasive occurrence of insufficient vitamin D levels . A european carotenoid database to assess carotenoid intakes and its use in a five-country comparative study. Melatonin prevents deterioration of erectile function in streptozotocin-induced diabetic rats via sirtuin-1 expression. Lutein dietary supplementation attenuates streptozotocin-induced testicular damage and oxidative stress in diabetic rats. Similarly, in women testosterone concentrations are lower in depressive patients when compared to healthy controls (Kumsar et al., 2014). In depressive disorders with decreased libido and low testosterone, the androgen hormone replacement therapy was at least as effective as serotonin reuptake transporters (Kranz et al., 2014). Although the depressive disorder is more prevalent in females (Bebbington, 1996) when compared to males, the prevalence of depression in males increases with age (Khera, 2013) as plasma testosterone drops. However, a very important study in rhesus monkeys showed that pharmacological castration reduced and testosterone supplementation normalized anxiety levels (Suarez-Jimenez et al., 2013). He used anabolic steroids for 8 months (January–August 1992), alternating 16-week cycles of testosterone cypionate (DepoTestosterone) at 1500 to 1800 mg per week, and oxymetholone (Anadrol) at 560 mg per week. For patients who could not recover spermatogenesis, the mean age was 44 years with a median duration of TRT of 4.0 years. In this case, it is crucial to understand which drugs can restore endogenous testosterone and sperm production. Several months or years after initiation of TRT, patients might want to have kids. Generally, patients are not aware of the long-term repercussions of TRT with regard to spermatogenesis. It has been demonstrated in animal models that olive oil supplementation significantly increased sperm quality 5,42. One reason why the Mediterranean dietary pattern is so positive for male fertility is because it provides a low level of SFA and trans fatty acids and adequate levels of certain nutrients such as omega-3 fatty acids, antioxidant molecules, and vitamins. Germ cells and mature spermatozoa are susceptible to oxidative stress, which leads to a decrease in sperm quality (decrease in sperm number and motility and increase in abnormalities in sperm morphology) 41,42,43. Increased amounts of adipose tissue cause insulin resistance and have an important role in the development of oxidative stress, thus altering reproductive pathways and sperm function 29,30. It is significant to emphasize that since this study reviews already published studies pertaining to patient data, ethical approval is not necessary. The increase in sex steroid production during puberty speeds up bone mineral accumulation and causes sex-specific variations in bone growth; after mid-puberty, the male population experiences a greater increase in periosteal bone growth than the female population, who shows more pronounced endocortical bone formation . Libido, or sexual desire, is significantly influenced by testosterone, which regulates various brain regions involved in sexual motivation, including the hypothalamus; in men, testosterone plays a crucial role in sexual desire and arousal . DHT has a stronger androgenic effect and is essential for the maintenance of prostate health and the development of secondary sexual traits in men . Such reduced pituitary FSH stimulation could adversely affect Sertoli cell function, inhibin B, and sperm production, as well as Leydig cell testosterone production. Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting an association between nutrition and male fertility. Nevertheless, also according to the numerous published studies and animal experiments, testosterone seems to affect brain functions. When testosterone is injected into the hippocampus together with a protein synthesis inhibitor that prevents genomic effects, spatial memory is improved in male rats (Naghdi et al., 2005). The metabolism of testosterone makes studying the physiology of testosterone effects on the brain difficult. Men with lower serum 25(OH)D levels, particularly those below 25 nmol/L, tended to have lower total and bioavailable testosterone levels compared to men with higher serum 25(OH)D levels. Chen et al. conducted an MR analysis on a cohort of 4254 Chinese men to explore the potential causal relationship between vitamin D deficiency and testosterone levels . The presence of VDR in the male reproductive system suggests that vitamin D may play a role in the synthesis of male reproductive hormones . In recent years, there has been a growing interest in investigating the potential influence of vitamin D on androgens, particularly testosterone levels, in men . In the RCTs, testosterone levels were measured after 12 weeks of vitamin D supplementation 1,22. If you are already on testosterone replacement therapy or taking an over-the-counter supplement, the doctor may recommend discontinuing treatment. If the supplement pushes levels too high, the body may actually not produce quality sperm. This primary sex hormone plays a role in everything from being interested in sex to producing enough healthy sperm to encourage fertilization during sex. These health consequences underscore the importance of addressing vitamin D deficiency as a pressing public health issue that impacts both individual well-being and healthcare systems on a global scale. The included studies consisted of four cross-sectional studies, three randomized controlled trials (RCTs), and one analysis utilizing Mendelian randomization. Out of these, eight studies fulfilled the inclusion criteria and were ultimately incorporated into the final review. Male obesity can dysregulate hormones in the hypothalamus–pituitary–gonadal axis (HPGA), causing secondary hypogonadism 15,17,18. The mechanisms by which obesity impairs male reproductive capabilities are multifactorial and interrelated. Meta-analyses have also concluded that higher BMIs in males correlated with a decrease in fertility and in vitro fertilization (IVF) success 10,11. Several population-based studies have demonstrated an association between Body Mass Index (BMI), MFI, and subfecundity, defined as time to pregnancy or lack of conception after ≥12 months of unprotected intercourse . Results—GLP-1 receptors have been identified within the male reproductive system according to the existing literature. FSH levels increased from 0.47 to 1.59 after 6 months and to 2.6 IU/L after 12 months, and LH levels from 0.2 to 1.17 after 6 months and 1.47 IU/L after 12 months of HCG therapy . One study showed that older age and a longer duration of TRT decrease the chances of sperm recovery (based on the criterion of a total motile count of 5 million sperm) at 6 and 12 months in testosterone-induced infertile men . After 6–12 months of treatment, all patients could ejaculate, and spermatogenesis was recovered in 71% of the patients . Although complex carbohydrates have been shown to offer multiple advantages in terms of overall health, there are no studies about their role in the preservation of male reproductive potential. Sperm mitochondria are a common target of oxidative stress and testosterone levels, which decreased their functionality. Increased blood glucose levels were also accompanied by a decrease in testosterone levels and an increase in oxidative stress . As reported before, low testosterone levels are strictly related to oxidative stress and to mitochondrial dysfunction (Figure 2). Recent studies demonstrated that also the administration of MUFA counteracted the negative effects of a hyperlipidic diet on sperm quality. Another study examined the antioxidant effects of pravastatin in a cohort of hypertensive and normotensive Wistar rats. Animal model studies have assessed the anti-oxidative effects of pravastatin following the induction of different disease states. Upon treatment, fluvastatin was found to decrease the effects of H2O2 on the neuronal cells in a dose dependent manner . A more recent study in 2021 by Wang et al., evaluated the anti-oxidative effects of fluvastatin on neuronal cells. In the intervention group, there was a significant decrease in SHBG levels after the intervention, potentially indicating an increase in the availability of FT, the biologically active form of testosterone. Notably, the study revealed a significant increase in SHBG levels in the placebo group among men with lower vitamin D status, while SHBG levels remained unchanged in the vitamin D group . Additionally, the timing of testosterone measurement can introduce variability as testosterone levels fluctuate throughout the day. These findings imply that maintaining sufficient vitamin D levels could potentially play a role in supporting testosterone levels. Furthermore, a cross-sectional study conducted by LM Wentz et al. in 796 US male soldiers and veterans revealed a high prevalence of inadequate vitamin D levels among male military personnel. Two authors (PMM and GRT) analysed the studies for quality assessment consensually. The quality assessment of the included studies was performed using the Newcastle–Ottawa Scale (NOS). Meta-analysis was performed if two or more studies or datasets reported data from the study and comparison group. Synthesis of results - AAS users had reduced levels of FSH and LH than the naïve population.First, the amount and quality of the nutrients introduced can affect sperm quality by acting on sperm energetic metabolism.Endurance exercise and conjugated linoleic acid (cla) supplementation up-regulate cyp17a1 and stimulate testosterone biosynthesis.In line with these findings is the lack of an association between actual salivary testosterone levels and mental rotation in men and women (Puts et al., 2010).Min Y, Sun T, Niu Z, Liu F. Vitamin c and vitamin e supplementation alleviates oxidative stress induced by dexamethasone and improves fertility of breeder roosters.A more recent study in 2021 by Wang et al., evaluated the anti-oxidative effects of fluvastatin on neuronal cells. The decreased intra-testicular testosterone combined with the suppression of FSH leads to decreased germ cell survival and maturation (Fig. 1). Spermatogenesis is largely dependent on the action of FSH on Sertoli cells coupled with high intra-testicular testosterone concentrations. GnRH in turn stimulates the release of LH and FSH from the anterior pituitary which modulates testosterone production from the Leydig cells and spermatogenesis by the Sertoli cells, respectively. In healthy adult men, testosterone production is precisely regulated by the HPG axis. A randomized, open-label, fixed dose, active control, phase IIB proof-of-concept study was designed to evaluate fertility in men with secondary hypogonadism who previously had been treated with 1% testosterone gel for at least 6 months. These studies indicate that low-dose hCG may be beneficial for men requiring testosterone supplementation therapy during their reproductive years and that intramuscular or transdermal TST does not necessarily significantly impact spermatogenesis. Intramuscular human chorionic gonadotropin (hCG) therapy is an option shown to protect against, or at least to diminish, the impact that exogenous testosterone has on intratesticular testosterone levels. A known critical element in the development of healthy spermatogenesis is high intratesticular testosterone.13 In men using exogenous testosterone, these levels can be greatly diminished. ASRM briefing united lawmakers, physicians & patients on IVF access, exposing RRM limits and urging policies to expand fertility care options. ASRM PRIMED cohort meets Congress to push for IVF access, clarify risks of restorative reproductive medicine, and defend science‑based fertility care. About 20% of infertility cases are due to a male factor alone. Fertility specialists for males will prescribe these drugs, because sometimes they can act to lower sperm counts if they are used incorrectly. Nutrients such as L‑arginine (a NO precursor) and omega‑3 fatty acids improve endothelial function. Systematic reviews cite a dose‑response relationship, where 200–300 mg daily yields measurable improvements in sperm concentration and morphology, particularly when combined with antioxidant vitamins. Therefore, a male enhancement product for humans that includes zinc may aid hormonal balance, but its effect is contingent on individual endocrine status. Animal models reveal that zinc deficiency diminishes Leydig cell activity, whereas supplementation restores serum testosterone within weeks. Zinc, selenium, and vitamin E function as enzymatic cofactors (e.g., superoxide dismutase for zinc) or direct free‑radical scavengers. They observed a decrease in sperm DNA fragmentation at the end of the study along with a significant increase in the testosterone/oestradiol ratio . These studies underscore the potential of liraglutide as a treatment option for hypogonadism, especially in patients who may also benefit from improved glycemic control . Participants treated with liraglutide exhibited markedly higher total serum testosterone levels than those who did not receive this treatment . Physicians treating hypogonadism should be aware of all these options and make the right decision based on the needs and conditions of each patient. After a month of therapy with clomiphene, 50 mg orally per day, no improvement in potency or libido occurred, but morning erections started. In July 1993, one year after his steroid use, he displayed a reduced testicular volume of 10 mL on both sides and 2 cm of gynecomastia on both sides. This might be related to the tasks used, as the testosterone levels in men are related to the learning strategies, especially for spatial memory (Choi and Silverman, 2002). In line with these findings is the lack of an association between actual salivary testosterone levels and mental rotation in men and women (Puts et al., 2010). Spatial cognitive abilities as well as general cognition and memory decline with aging together with the testosterone levels. Sertoli cells were found resting on the thin basal lamina (basement membrane) while the spermatogenic cells were arranged in many layers (spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids, and sperms). The results indicated a significant, dose-dependent increase in NFκB content across all PS-MP-treated groups compared to the control group. Changes in testes mitochondrial function, apoptotic, and inflammatory markers; (a) TFAM, (b) PGC-1α, (c) UCP1, (d) caspase-3 activity, (e) NF-κB. The results indicated that glutathione levels (GSH) and total antioxidant capacity (TAC) showed a significant dose-dependent decrease in all groups administered with PS-MPs compared with the control group, as shown in (Fig. 4b, c). The first stages of puberty are usually normal and characterized by some virilization and an increase in serum T concentrations into the pubertal range, followed by a rise in gonadotropin levels and a plateau in circulating T . The diagnostic dilemma between CDGP and HH may be addressed clinically with 3 to 6 months of T therapy to induce pubertal maturation. Measurements of inhibin B and antimüllerian hormone, both markers of Sertoli cell number, and insulin-like factor 3, a marker of Leydig cell function, have been proposed as diagnostic tools 102, 113, 114. Basal gonadotropin and gonadotropin-releasing hormone stimulation tests have limited diagnostic specificity, with an overlap in gonadotropin levels between CDGP and HH . The consumption of fruit, vegetables, fish, processed meats, dairy products, sugars, alcohol, and caffeine importantly impact on male fertility. In addition, nutrients affect sperm production and spermatogenesis, controlling sexual development, and maintaining secondary sexual characteristics and behaviors. Hormones are strongly influenced by the nutritional status of the individual, and their alteration can lead to dysfunctions or diseases like infertility. Age, sex, current endocrine status, but also the timing of testosterone analysis or administration, status of the target tissues and several other factors influence the outcome of observational or interventional studies. A survey of over 9,000 men from different populations in 2005 found that 29% to 71% of men are interested in using a form of hormonal male contraception 22,23. As it is a user-dependent method, many couples seek easier to use options like female oral contraceptive pills or intrauterine devices . This effect may diminish with the cessation of testosterone intake, but the extent of recovery is not clear for chronic users 16,19. These assistive reproductive technologies are expensive and are not always successful 17,18. Disrupted hormone exposure leads to conditions like micropenis and other genital abnormalities. A number of things can disrupt hormone exposure, including endocrine-disrupting chemicals. It’s true that testosterone impacts penile growth. ” In this quick guide, we’ll discuss how testosterone impacts penile development through the lifespan. These results are supported by another study that reported no significant change in sperm parameters after assessing the effect of pravastatin on adrenocortical and testicular steroidogenesis . A study by Farsani et al. examined such properties on a cohort of 24 healthy male Sprague–Dawley rats that were exposed to doxorubicin. Although no studies have evaluated the effects of fluvastatin on sperm parameters, the aforementioned studies were still able to demonstrate the beneficial antioxidant effects of fluvastatin. A study showed that fluvastatin administered with vorinostat for renal cancer had positive effects, showing that mTOR expression was increased in human models . Furthermore, since atorvastatin influenced the sperm capacitation adversely, this could lead to pernicious influences on male fertility, as capacitation is the key for fertilization to occur. However, these levels on average did not reach below normality, with the exception of Kannat et al. 2009 data, which were already below normality before starting the medication (46). However, this analysis was hampered due to the low number of articles and patients evaluated, shown in the GRADE evidence summary. Twenty-one articles were included with a total of 9,879 patients evaluated. Thus, in order not to commit any ecological fallacy, it was only accepted as significant evidence, the analyzes that, when there were population studies, had their statistical result in agreement with the prospective studies. “If you take one of these medications to treat hair loss, the data is conflicting about the impact on sperm production,” Dr. Vij says. Their impact on your fertility is usually mild and will reverse once you stop the medication, but while you’re taking them, it could be more difficult for you to create a pregnancy. The most likely outcomes are a very low sperm concentration or a complete absence of sperm from the semen. But opioids are highly addictive, so turn to your healthcare provider with any concerns you might have about responsible short-term use or past issues with addiction. Short-term use hasn’t been shown to have a negative effect on fertility, like if you’re on a short course of opiates to control pain after surgery or a broken bone. Jensterle et al. also highlighted the correlation between the degree of weight loss and the magnitude of testosterone increase, aligning with previous studies that established a relationship between weight loss and total testosterone levels 58,64.Gastrointestinal symptoms, including nausea, vomiting, and diarrhea, are the most commonly reported side effects .Testosterone, Follicle-stimulating hormone (FSH), and Luteinizing hormone (LH) were determined using rat-specific ELISA kits (Cusabio, USA, with Catalog No. CSB-E05100r, CSB-E06869r, and CSB-E12654r, respectively).Different findings suggest that sperm mitochondria play a pivotal role in the decrease of sperm quality caused by ROS.The TRT literature on adolescent males is limited on T-induced pubertal changes and growth.Although no studies have evaluated the effects of fluvastatin on sperm parameters, the aforementioned studies were still able to demonstrate the beneficial antioxidant effects of fluvastatin.In order to make treatment and compliance more realistic and sustainable, testosterone-enhancing therapy would also come in a form that allowed for a convenient and acceptable route of administration, preferably in pill form. While AAS use for performance enhancement is not a new phenomenon, it has detrimental impact on male fertility parameters such as reduced gonadotropin levels and sperm concentration. In addition, the long-term effects of AAS on male fertility remain inadequately studied, as some studies focused on short-term outcomes only. TT values at baseline, end of cycle, 3 months and 1-year testosterone levels were 10.60, 23.01, 4.26 and 4.49 ng/ml, respectively. For example, men on long-term testosterone replacement therapy may have a higher risk of heart problems. However, this form of testosterone therapy may also be used later in life for transgender men. The majority of men prescribed testosterone for low levels are at least 50 years of age or older. Evidence to suggest that TRT increases cardiovascular morbidity and mortality risks is poor, as results vary across study populations and their baseline comorbidities.Changes in testes mitochondrial function, apoptotic, and inflammatory markers; (a) TFAM, (b) PGC-1α, (c) UCP1, (d) caspase-3 activity, (e) NF-κB.The shared membership of VDR and testosterone in the nuclear receptor family underscores the significance of understanding their interaction.A possible mechanism can include the androgen receptor, as its blockade has been shown to prevent the testosterone-induced anxiolysis.It’s the first step in detecting male fertility issues.However, HCG alone probably triggers similar increases in serum testosterone levels.Our understanding of the relative advantages of both physiological and pharmacological therapies for aging men is greatly improved by the effects of testosterone treatment and exercise on factors such as strength, aerobic fitness, and body composition .Even a short 6-week testosterone treatment resulted in improved spatial and verbal memory of older men (Cherrier et al., 2001).While the American Urological Association guidelines endorse the use of aromatase inhibitors for individuals with low testosterone, current support for treating idiopathic infertility in men primarily revolves around follicle-stimulating hormone analogs . After histological examination, they found a significant difference between testicular injury in the IR group and the atorvastatin group. Administration of atorvastatin commenced after the first day of the busulfan therapy and was continued for 28 days. For example, a low dose of atorvastatin may have an anti-inflammatory effect and antioxidant properties 58,59, while a high dose of Atorvastatin may negatively alter sperm motility and morphology 47,60. The data indicate a significant and dose-dependent increase in caspase-3 activity across all PS-MP treatment groups compared to the control group. Figure 5d presents the changes in testicular caspase-3 activity, an established apoptotic marker, in adult male rats following oral administration of various doses of PS-MPs(0.1, 1, 10, 20, and 40 µg/kg BW). The data from the present study (Fig. 5a-c) illustrate the dose-dependent changes in the expression of TFAM, PGC-1α in the testes, and UCP1 in adult male rats. In contrast, the percentage of abnormal sperm showed a significant dose-dependent increase in all treated groups relative to the control group (Fig. 3e). Conversely, FSH and LH levels exhibited a significant dose-dependent increase in all PS-MP-administered groups (Fig. 3a and b, and 3c). Therefore, it has been suggested that Vitamin E improves mitochondria activity, decreasing the damage to sperm and mitochondria 90,111. Vitamin E is found in plant-based oils, nuts, seeds, fruits, and vegetables and acts as an antioxidant, defending the organism against oxidative stress, thus having an important role in the protection of sperm membranes against ROS and lipid peroxidation. The main antioxidant vitamins that help regulate free radicals in male reproduction are Vitamin E and Vitamin C 90,110. Therefore, as multi-functional endocrine disruptors, they interfere with the enzymes needed for steroid biosynthesis and/or degradation . Exposure to MPs has been shown in other research to disrupt spermatogenesis and gonadotropin-releasing hormone (GnRH) levels in male rats, and to induce both metabolic abnormalities and generational abnormalities in mice24. Additionally, it may disrupt the medaka’s hypothalamic-pituitary-testicular axis, which could lead to aberrant blood levels of sex hormones and reproductive endocrine abnormalities21. Researchers have shown that after acute and short exposure to MPs, testes exhibited oxidative damage, abnormal levels of hormones, and reduced sperm quality9. Therefore, understanding the precise effects of MP exposure on the male reproductive system and sperm remains a crucial research priority1,2. 2. Effects of cigarette smoking on Zn levels of seminal plasma: In a study on opposite sex twins, it has been demonstrated that also the etiology of depression is different in men and women (Kendler and Gardner, 2014). Further it was investigated that testosterone can modulate serotonergic transmission, where serotonin plays a crucial role in depression development (Jovanovic et al., 2014). Some of the animal experiments on testosterone and anxiety are summarized in Table 1. But in general, experiments on monkeys are more relevant to human behavior and, thus, this study must not be overseen. Implants that slowly release testosterone totally ignore daily variations that occur physiologically. In some studies, even the best-known circadian rhythm is not taken into account. The concentration in the hair might, however, be relevant as it integrates all the intra-individual variability of testosterone (Dettenborn et al., 2013). There are several possibilities as to what kind of biological samples should be used for the testosterone measurement. Other possible explanations might be due to low number of animals included, but also to physiological differences including body size and the concluding testosterone kinetics (King et al., 2012). One observation that should be considered is the increase in prostate volume demonstrated in the studies by Page and Yassin and colleagues described above. While this study also demonstrates the desired effect of decreasing prostate volume, it failed to demonstrate any significant improvement in symptom scores or objective measures of urinary function. The supportive argument posits that by treating men with TRT, thereby increasing PSA levels and administering T to a steroid responsive cancer, a man’s risk of development of prostate cancer is significantly increased. Similarly, previous studies showed that PS-MPs treatment using higher doses disrupts spermatogenesis, causing irregular arrangement of spermatogenic stages, reduces sperm motility, viability, and normal morphology, while increasing sperm malformations and dead cells43,44,45. The study provides solid evidence of the dose-dependent reproductive toxicity of oral exposure to polystyrene microplastics (PS-MPs) at doses ranging from 0.1 to 40 µg/kg body weight, in male rats. Histopathological study showed that the cycle of spermatogenesis was regular in all male rats in control (Fig. 1A). The results revealed increased oxidative stress levels in adult male rats following oral administration of varying doses of polystyrene microplastics (PS-MPs) (0.1, 1, 10, 20, and 40 µg/kg BW). Changes in reproductive hormones in plasma (a) Testosterone, (b) FSH, (c) LH, and semen characteristics; (d) Sperm count, (e) Abnormal sperm, (f) Sperm motility. While further studies are necessary, the current literature elucidates that GLP-1Ras emerge as a potentially promising therapeutic avenue for improving semen parameters in obese men. Beyond the initial 8-week diet intervention, liraglutide did not have additional effects on semen parameters . This improvement was maintained after one year, but only in individuals who maintained at least a 12 kg weight loss, regardless of their treatment group. At the start, 17% of participants had oligospermia which decreased to 13% after the 8-week intervention, further supporting the link between weight loss and improved sperm parameters . Comparatively, the European Male Aging Study, a population-based prospective cohort study of 3369 men aged 40–79 years from the general population of eight European countries, reported an age-adjusted annual decline in total T of 0.4% per year Wu et al. 2008. The Massachusetts Male Aging Study, a community-based study of 3339 random men aged 40–79 years reported an annual decline in total and free T of 0.8–1.6% and 1.7–2.8% per year respectively in men over 40 years of age Mohr et al. 2005. Between 2001 and 2011, prescriptions for TRT among men 40 years of age or older in the US increased more than threefold, from 0.81% in 2001 to 2.91% in 2011 Baillargeon et al. 2013. TRT may result in erythrocytosis in some men, however long-term studies have not reported significant adverse events (e.g. cerebrovascular accident, vascular occlusive events, venous thromboembolisms). In 1-year analysis, the baseline population was the one who was yet to start AAS use in prospective observational study Figure 2. Heterogeneity in all these studies was substantial, but lowest at 1-year follow-up. Effects of stopping AAS on FSH at various intervals were evaluated in different studies. In contrast to the findings of Chen et al., the study found no association between vitamin D-related gene polymorphism and hormonal levels. Additionally, the association between serum 25(OH)D and bioavailable testosterone was only significant for men with very low vitamin D levels (26]. Additionally, only a small percentage (2.7%) of the study subjects in Chen et al.'s study exhibited severe vitamin D deficiency, limiting the ability to establish a direct correlation between severe vitamin D deficiency and testosterone deficiency . Several studies have investigated this relationship, providing valuable insights into the complex interplay between vitamin D and testosterone. Several studies suggested the hypothesis that decreased Zn concentration can lead to an increase in oxidation of DNA, proteins and lipids which underlined Zn main role in prevention of oxidative damage. A small amount of ROS is essential for sperm to obtain fertilizing capabilities, but high seminal ROS levels may reduce the effective concentration of seminal Zn (59). Zn is a necessary component of Cu/Zn superoxide dismutase, which has antioxidative activity for sperm function (56). Zn sulfate treatment in serum and seminal plasma level of anti-sperm antibody (ASA) have result in a significant enhancement of the seminal fluid parameters including sperm concentration, sperm motility, vitality and normal sperm morphology (52). On the other hand, other studies have observed no significant association between Zn and semen quality parameters (12, 45). Most studies utilized morning blood samples to assess serum testosterone and vitamin D levels. The study participants were adult males aged 18 years and above, and sample sizes in these studies ranged from 62 to 4254. Furthermore, it aims to evaluate the potential impact of vitamin D supplementation on testosterone levels. Of particular interest is the potential interaction between vitamin D and testosterone, a vital hormone in adult males. To establish more definitive evidence regarding the impact of vitamin D on testosterone levels, there is a need for further well-designed, long-term RCTs that encompass diverse populations. After treatment, the HCG group displayed significantly higher serum concentrations of 25-OH-vitamin D and significantly lower serum concentrations of estrogens, hematocrit, PSA, and prostate volume compared with testosterone. Topical testosterone gel is also on the milder side with regard to fertility issues. FSH levels decreased by 52% in the testosterone gel group, and by 27% in the 2 mg and 37% in the 4 mg progestin groups . One study investigating the contraceptive effectiveness of topical testosterone gel vs. progestin demonstrated that 10 g of testosterone gel (1%) daily for 20 days inhibited LH and FSH to a greater extent compared with 2 or 4 mg of progestin alone . Compared with initial values, LH (from about 3 to 1 IU/L) and FSH (from about 5 to 2 IU/L) levels significantly and chronically decreased for the duration of the intervention without additional improvements after 6 months. Adequate Zn content of seminal plasma is needed for men’s health, germination, normal sperm function and fertilization. Similarly, Zn treatment induces an increase in cellular Bax levels and Bax/Bcl-2 ratio would bolster the Zn influence on mitochondrial Bax. The investigators of this study defined that, due to the ability of Zn to enhance Th-2 cytokines and down-regulate Th-1 cytokines, Zn may moderate the putative effects of cadmium on spermatogenesis (31, 65). A number of studies have shown that cigarette smoking has a harmful effect on sperm quality, most significantly sperm concentration, motility and morphology; however, some studies have found no relationship between smoking and sperm parameters. Increased ROS levels in the seminal plasma of infertile men may decrease Zn concentration, increasing detrimental effects of ROS to sperm cells that are correlated with abnormal sperm parameters (Figure 1). A case report by Tada et al. showed that rosuvastatin was able to cause reversible azoospermia in a patient seeking fertility treatment. The studies that reported the adverse effects of rosuvastatin were performed on healthy rats while the studies that showed beneficial effects were carried out on diseased animals. Following treatment, comparable measures of FSH and LH levels were observed; however, there was a decrease in testosterone. In animal models, Leite et al. evaluated the effects of rosuvastatin on male fertility in a cohort of Wistar rats. With rosuvastatin being one of the most effective statins in managing hypercholesterolemia , it is essential to evaluate its effects on male fertility. When publication bias and the high intra- and inter-individual variability of testosterone are taken into account, these small negative or contradictory studies could be even more important. At least in one small study, depressive women had higher testosterone (Weber et al., 2000). At least in one published randomized controlled trial, the effects of testosterone were comparable to placebo effects (Seidman et al., 2001). Despite its positive effects on sexual function, it has a negative effect on fertility.A study showed that fluvastatin administered with vorinostat for renal cancer had positive effects, showing that mTOR expression was increased in human models .There was a decrease in Free Testosterone in the cross-sectional study, but no statistical difference was seen in prospective studies, as there was an important decrease in the number of studies that analyzed the variable.HCG has also been used (often with clomiphene citrate, tamoxifen or anastrozole) because it stimulates the production of endogenous testosterone without compromising spermatogenesis.While bodybuilding products can have many positive effects on overall health and fitness, men should be aware of the potential effects of supplements on male fertility.In the present study, rats received 0.1–40 µg/kg/day PS‑MPs by oral gavage, i.e., doses that are 10–1000‑fold lower than the mg/Kg ranges frequently employed in rodent microplastic toxicology studies.These µg/kg doses fall within or below upper‑bound estimates of human and wildlife microplastic exposure.Conversely, diets rich in processed meats, soy, potatoes, full-fat dairy products, coffee, alcohol, sugary drinks, and sweets seem to worsen semen quality 12, 14 (Fig. 2).In a singular case report in a patient with idiopathic infertility and initially normal semen parameters, a notable transition to severe oligospermia and later azoospermia occurred after a 4-month period. How to reduce your risk Thus, the local production of estrogen centrally, by means of aromatization of T, is crucial for the stimulation of sexual desire in men. However, it is still a matter of debate whether or not the effect of T on sexual desire is due to the activation of the androgen receptor (AR) present in several areas of the human brain. After adjusting for the other two variables, the highest likelihood ratio (Wald test) for low T is with low sexual desire, while loss of erection (either spontaneous or sexual related) is better explained by an older age or by high CDS scoring. To confirm this point we simultaneously introduced quintiles of the three variables (age, T and CDS) in a binary logistic model in order to explain moderate or severe sexual symptoms (Table 1). They found that rosuvastatin altered epididymal morphology, caused a delay in ejaculation, and as well a reduced fertility potential after natural mating . The two groups treated with rosuvastatin also displayed an increased tendency to abnormal seminiferous tubules with increased acidophilic cells. It has an additional stable polar methane–sulphonamide group which increases its interaction with HMG-CoA reductase and decreases the lipophilicity of the drug, making it unlike any other statin . Taken together, larger studies with humans are needed to reach any definitive conclusions. However, from an animal studies standpoint, pravastatin may have some anti-oxidative effect when subjected to an external stressor. These ancillary drugs stimulate endogenous testosterone production and therefore help prevent a complete shutdown of the HPG axis. The sperm concentration significantly improved from 4.7 × 106/mL to 13.1 × 106/mL and the total motile count from 4.6 × 106 to 8.0 × 106 . One study recruited subfertile hypoandrogenic men with low T/estradiol (E2) ratios . The testolactone group had an improvement in the testosterone-to-estradiol ratios. Moreover, an improvement in virilization, libido, and erectile function was also noted . The effectiveness of this drug in controlling cholesterol production is impeccable, however, patients often complain of a variety of side effects, such as myalgia, muscle atrophy, and in some cases, rhabdomyolysis.More research needs to be done to evaluate the contraceptive effect of the various formulations of testosterone.However, this was a small study and there is a need to verify the findings and better understand the functional implications of the observed changes in HDL constituent proteins .Fatty acids and several plant antioxidant molecules can target the mitochondria, improving and/or restoring their function, by acting on the ATP and ROS levels.ASRM PRIMED cohort meets Congress to push for IVF access, clarify risks of restorative reproductive medicine, and defend science‑based fertility care.In this context, unhealthy hypercaloric diets and excessive intake of saturated and trans fatty acids have a negative impact on sperm quality and, therefore, on the fertilization process 4,5,6,7,8,9,10,11.More recent advancements were shown in the 2018 Endocrine Society meeting, with dimethandrolone undecanoate shown to effectively decrease sperm counts without adverse effects in a double-blind study in 2 academic sites.Insomuch that Zn influences a man’s fertility, sex drive and long-term sexual health are influenced. Risk factors After two months of treatment, the latter was confirmed, finding a significant increase in androstenedione . After the first month of simvastatin therapy, no changes were observed in testosterone, dehydroepiandrosterone sulfate (DHEA-S), LH, and FSH, while a significant increase was noted in androstenedione. They administered simvastatin at 10 mg for the first six weeks of the study, followed by 20 mg for a further six weeks, and finally 40 mg until the end of the study (12 months) in a cohort of 10 hypercholesterolemia patients. Flanagan and Lehtihet reported dysfunction of hypothalamo–pituitary–gonadal axis (HPG) in the form of attenuated response to gonadotrophic releasing hormone and human chorionic gonadotropin (hCG) stimulation tests despite an AAS washout period of 7 months. In addition to these AAS, some subjects also used hormones such as growth hormones, antiestrogens, fertility agents, erectile dysfunction drugs and weight loss drugs. Medical Subject Heading (MeSH) terms and keywords such as ‘anabolic androgenic steroids,’ ‘male fertility,’ ‘testosterone congeners’ and ‘doping’ were used. Moreover, some recently published work on this issue did not perform meta-analyses.10,11 The purpose of the present meta-analysis and systematic review is to determine the effects of AAS on male fertility amongst AAS abusers compared with non-abusers. Thereafter, he continued treatment with clomiphene citrate for 2 months, leading to a total testosterone level of 705 ng/dL and an LH level of 26.3 mIU/L, and his symptoms resolved . FSH, LH, and free testosterone levels improved slightly, but not within the normal range. His serum gonadotropin and free testosterone levels were low, (0.6 mIU per ml for FSH, 1.9 mIU per ml for LH, and 7.1 pg per mL for free testosterone). Two months after the five days of clomiphene citrate administration, the symptoms came back, and his total testosterone level decreased again to 301 ng/dL. He started treatment with 100 mg of clomiphene citrate for 5 days, leading to a total testosterone level of 828 ng/dL 2 weeks later. Another similar case study showed the case of a 30-year-old male who abused several different types of anabolic steroids . In lieu of this, the findings of studies that have shown the reduced expression and malfunctioning of LDL-receptors in patients with familial hypercholesterolemia appear important 74,78. Another study reported that eight patients placed on different statins such as simvastatin, fluvastatin, pravastatin, and atorvastatin showed decreased libido during treatment. The study of Bruckert et al. showed that men treated with statins complained more frequently of erectile dysfunction, with further multivariate analyses showing that impotence was dependent on treatment with statins . The same authors, using the same cohort, also sought to evaluate body compositional and cardiometabolic effects of TRT with TU in men with obesity and severe OSA Hoyos et al. 2012b. Our literature search retrieved five studies that evaluated this association Barrett-Connor et al. 2008; Bercea et al. 2013; Hoyos et al. 2012a, 2012b; Killick et al. 2013. The potential risk of adverse effects of TRT on sleep, specifically OSA, has been a growing area of research and discussion. Current evidence does not support an increased risk for worsening LUTS with TRT, and some men may in fact experience mild symptomatic improvement. This study adds to the mounting evidence that suggests TRT may in fact improve LUTS; however, this study is limited in that men with severe LUTS by IPSS and evidence of obstruction were excluded. In the present study, rats received 0.1–40 µg/kg/day PS‑MPs by oral gavage, i.e., doses that are 10–1000‑fold lower than the mg/Kg ranges frequently employed in rodent microplastic toxicology studies.These µg/kg doses fall within or below upper‑bound estimates of human and wildlife microplastic exposure. PS-MPs trigger inflammation and apoptosis, evidenced by increased NF-κB and caspase-3 expression, and impair mitochondrial function by altering the expression of PGC-1α, TFAM, and UCP1. Figure 5e presents the changes in the testicular concentration of NFκB, an inflammatory marker, in adult male rats following oral administration of various doses (0.1, 1, 10, 20, and 40 µg/kg BW) of PS-MPs. Preventive interventions have socioecological strategies involving ethics, principles, values, social norms, body image and healthy alternatives aimed at bodybuilding. The present review suggested that men who are unaware of negative impact of AAS on fertility are likely to regret AAS use. As most of the AAS use is uncontrolled and unregulated, the exact effect on fertility is difficult to evaluate. The current review has shown that higher T doses are protective for erectile functions during their use, but there can be decreased libido and ED after discontinuing T. However, prior literature has failed to definitively demonstrate an increased risk in a cause-and-effect relationship. The theoretical relationship between an increased risk of prostate cancer development and TRT has been a robust debate for decades. The Saturation Model postulates that the androgen receptors on the prostate are saturated at physiologic and even subphysiologic levels of T, such that there is minimal response of the prostatic tissue to TRT. To date, there are no prospective studies that have evaluated the risk of VTE in men receiving exogenous T supplementation. Although the influence of statins on fertility is not widely investigated, multiple studies have demonstrated their effects on fertility. Therefore, we recommend that future studies should investigate how these adverse effects are exerted, aside from the causation of reduced steroid hormones. From the available evidence, although inconclusive, the findings have shown that some forms of statins can cause testicular dysfunction owing to their ability to reduce testosterone production. Some studies suggest synergistic effects when antioxidants, cofactors, and mitochondrial agents are combined, yet others highlight difficulty isolating the active component and increased risk of interactions. Human data are less consistent; a 2022 meta‑analysis of nine randomized controlled trials (RCTs) concluded that zinc supplementation modestly increased testosterone (mean change ≈ 0.8 nmol/L) only in men with documented low baseline levels. Supplements intended to increase male fertility encompass a heterogeneous group of vitamins, minerals, amino acids, and plant‑derived compounds. Considering the prospective benefits of testosterone therapy, more investigation and clinical testing are necessary to completely comprehend its effects and improve therapeutic modalities. At days 0, 15, 30, 45, and 60, male rats were paired with four females to stimulate mating. After 16 weeks of withdrawing from rosuvastatin intake, sperm was seen in the semen, making IVF possible . As seen in the previously discussed forms of statin, the contradictory outcomes in these animals’ studies are plausibly due to variability in disease conditions. Rosuvastatin reduced the levels of caspase 3, NF-κβ, and iNOS induced by high glucose levels, possibly owed to the anti-oxidative properties of rosuvastatin . The evaluation showed that diabetic rats displayed testicular degeneration and necrotic seminiferous tubules. Well, it already does as part of natural body processes—testosterone is one of several hormones that helps your penis grow both in utero and during puberty. Rat studies again suggest that testosterone deficiency (for whatever reason) or exposure to disruptive chemicals throughout childhood and adolescence can also inhibit post-natal penis growth. Then, testosterone and growth hormone together drive penis growth. Research with rats suggests that your eventual penis size is mostly determined in utero by hormone exposure (including testosterone) during a critical period. We’ll also discuss whether supplemental testosterone can increase the size of your penis. Adverse effects of testosterone replacement therapy: an update on the evidence and controversy The complications of untreated hypogonadism differ depending on whether it starts in the womb, at puberty or in adulthood. If any of these risk factors are in your family health history, tell a member of your healthcare team. At times, primary and secondary hypogonadism occur together. This is called acquired hypogonadism. A trait passed through families, also called inherited, can cause either type of hypogonadism. Castration and supplementation with testosterone had no effect when the photoperiod was long (16 h of light per day). In diabetic rats, the memory impairment was partially reversed by testosterone administration as well (Nayebi et al., 2014). In castrated rats, testosterone was able to reverse the ethanol-induced memory deficit (Khalil et al., 2005). Testosterone has very likely an important role in the physiology of brain functions, but it might also be useful in some pathologies. When dihydrotestosterone—the androgen metabolite of testosterone was injected into the CA1 region of the hippocampus, spatial memory was improved (Babanejad et al., 2012). PGC‑1α and TFAM are key regulators of mitochondrial biogenesis; their suppression in testicular tissue suggests reduced mitochondrial mass and impaired maintenance of the mitochondrial network in germ cells64,65. In our study, at the mitochondrial level, the oral exposure to low doses of PS-MPs induced a significant downregulation of the expression of, PGC-1α and TFAM, while significantly upregulating the expression of UCP1. According to Wei et al., ROS and MDA levels in the testes were significantly elevated after being exposed to PS-MPs, while dramatically lowering the levels of GSH. Rogol et al retrospectively evaluated the clinical response to T gel 1% in a subgroup from a prospective, open-label, observational study of 86 adolescent boys (age years) with primary hypogonadism due to Klinefelter syndrome or anorchia. These studies provide significant evidence that short-term use of oral TU at 40 mg daily is safe and effective to promote growth and pubertal changes without an adverse effect on bone age in adolescent males with CDGP . Similar effects on growth and pubertal maturation were observed in a larger, retrospective study of 96 Danish boys treated with TU daily (40-mg daily doses escalated up to 80 mg twice daily) for an average of 0.8 years and 63 untreated controls . Earlier forms of oral testosterone (methyltestosterone and 17α derivatives) led to hepatic dysfunction and are no longer marketed . These findings suggest potential influences of vitamin D supplementation on hormonal balance, particularly in individuals with impaired spermatogonial tests. While there is no significant impact on TT levels, notable changes in SHBG and FT levels have been observed within the intervention and placebo groups. However, it is important to note that the treatment group received weekly doses of 50,000 IU of vitamin D3 for eight weeks, followed by a maintenance dose of vitamin D3 (50,000 IU) once a month for the remaining four weeks. Of particular concern is their impact on male fertility; MPs have been observed to accumulate in mammalian reproductive organs, leading to documented negative effects on sperm quality. AAS-induced sexual dysfunction and hypogonadism are more common, usually temporary and require treatment with testosterone replacement therapy, SERMs and PDE5 inhibitors. Men with low testosterone may have sexual difficulties that interfere with fertility, but low testosterone levels may also interfere with normal sperm production. The likelihood of sarcopenia (age-related muscle loss) and diminished muscle strength rises as testosterone levels naturally fall with age; however, research indicates that testosterone therapy may mitigate these effects in older men, enhancing physical performance, sexual drive, and muscle mass . Testosterone, a steroid hormone predominantly synthesized in the testes, is integral to a wide range of physiological processes that are crucial to male health; the regulation of testosterone levels operates through a feedback mechanism that is essential for understanding its physiological control. Hence, available data clearly indicate that sexual health should be considered a mirror of general health, which, in turn, is a prerequisite to remaining sexually active. The same studies have clearly demonstrated that, according to psychological, organic and couple relationship modifications, occurring with advanced age, coital intercourse is not an essential prerequisite to remain sexually active 7, 8. TRT is effective in improving sexual function in middle-aged and older subjects but its role is small and extremely variable. The specific contribution of low T to sexual function impairment in aging men has still not been completely clarified. After 6–12 months of treatment, all patients could ejaculate, and spermatogenesis was recovered in 71% of the patients .Meta-analysis of follicle-stimulating hormone at various time intervals.In this study, proper dosing became an issue, given the variable responses in individual adolescents .Perhaps one of the reasons for this correlation is the existence of Zn in the nucleus and tail of early sperm for chromatin condensation and motility.Testosterone is required for sperm production, but the level in the testes where sperm is produced is many times higher than in the blood.” In this quick guide, we’ll discuss how testosterone impacts penile development through the lifespan.At the completion of the 68-week treatment plan, investigators found weight loss to be superior in the group that received semaglutide once weekly, with a mean weight change of −15.8% in this group .Interestingly, in the placebo group, there was a significant increase in FT levels , which contrasts with the findings of Lerchbaum Elisabeth et al., where the placebo group showed a significant increase in SHBG levels . Even with sufficient sperm concentration, it is crucial to prioritize the enhancement of sperm quality, ensuring more favorable outcomes for obese men undergoing IVF. This observed difference in telomere length likely contributes to poor sperm quality and overall inferior IVF outcomes in this demographic. Additionally, the study uncovered a noteworthy disparity in sperm telomere length, with obese men exhibiting shorter telomeres compared to the normal BMI group . Furthermore, despite clomiphene citrate’s association with significant increases in sperm concentration, it is not universally effective, with a meta-analysis indicating a significant increase in sperm concentration in approximately 60% of men . Although both are viable treatments for enhancing hormonal balance and semen parameters, clomiphene citrate has rare but documented side effects, including thromboembolism, gastrointestinal distress, and occasional weight gain in men . However, potential influences on sex hormone-binding globulin and free testosterone levels were observed. The effects of vitamin D supplementation on testosterone levels were inconclusive, with limited evidence of significant changes in total testosterone. Therefore, larger experimental and clinical studies are needed mainly on humans to draw any definitive conclusions on the effects of statins on male fertility. In fact, it has been shown that the intake of antioxidant vitamins and carotenoids was related to higher sperm counts . The Mediterranean diet incorporates the traditional healthy living habits of people from countries surrounding the Mediterranean Sea, although differentiated by some food choices and cooking practices. Therefore, ATP synthesis is severely affected, and the decrease in energy production results in meiotic arrest, causing the presence of abnormalities in sperm morphology. This study evaluated the dose-dependent effects of PS-MPs on adult male rats by assessing semen quality, reproductive hormones, oxidative stress, mitochondrial and inflammatory markers, and testicular histology. Here, we have highlighted the impact of the various food groups on reproductive hormones and on spermatogenesis, and the effects of classical and latest dietary patterns such as Mediterranean diet, Western diet, intermittent fasting, ketogenic diet, and vegan/vegetarian diet on male fertility. Sönmez M, Türk G, Yüce A. The effect of ascorbic acid supplemen-tation on sperm quality, lipid peroxidation and testosterone levels of male wistar rats. Due to the contradictory findings in the literature, the hypothesis of this study is that continuous use of statins may lead to decreased levels of testosterone and other sex hormones in patients with hypercholesterolemia, potentially resulting in hypogonadism. Accordingly, in another meta-analysis , the effect of an acute PhyEx on T levels was addressed. For low calorie diet, the effect was proportional to the degree of weight loss, reaching a 7 nmol/L increase in total T for a delta weight of 25 kg. Interestingly, training the MetS-rabbits to perform daily physical exercise (PhyEx) on a treadmill normalized gonadotropins and T levels and restored acetylcholine (Ach)-induced relaxation of corpora cavernosa and NO signaling within the penis . In addition, metaflammation –a tissue inflammation driven by metabolic disorders- was also observed within the testis and epididymis with a consequent impairment in steroidogenesis and spermatogenesis. We previously set up an animal model of MetS, feeding rabbits for three months with a westernized diet enriched in cholesterol . Enclomiphene citrate may represent an oral option for treatment of hypogonadism in younger patients who desire to raise testosterone levels, while also maintaining semen quality.20 Future phase IIIB studies are planned to verify the efficacy of enclomiphene citrate in maintaining semen quality. These findings are supported by another study that found that prepubertal rats exposed to rosuvastatin were at an increased risk of decreased testosterone levels and sperm quality, both hindering the onset of puberty and affecting fertility . Another study gathering data from more than 1000 healthy men with normal sperm production investigated the effects of 30 months of injectable testosterone undecanoate on fertility outcomes . Another study showed that 20 patients treated with TRT for erectile dysfunction and androgen deficiency for 4–12 months (with a median of 8 months) all recovered serum hormone levels and sperm concentrations (≥15 × 106/mL) after 2–11 months (with a median of 8 months) . Cardiovascular, metabolic, and sexual functions, bone and muscle mass, and mental health can be impaired if testosterone levels are low, while testosterone replacement therapy has been shown to improve these parameters 1,2,3,4. In a Chinese study of a monthly intramuscular TU injection, an azoospermia rate of 93% to 98% was achieved after 6 months with 1 million/mL as the criteria for effective suppression 25,26. The study found that regular testosterone use for 10 to 12 weeks causes suppression of sperm production, and even azoospermia, albeit inconsistently . Thirty percent of the 66 men were not able to achieve a total motile sperm count of more than 5 million after 12 months in the study. All men in these studies recovered to baseline levels after cessation of therapy; however, it took up to 2 years for some men to recover. Next, this study excluded 128 hypogonadal men (originally reported as 1132, of whom over 100 were actually women) who had suffered either MI or stroke, prior to initiation of T therapy. Men were excluded if they were started on TRT prior to angiography or prior to obtaining serum T levels, as ‘time 0’ was defined as time of angiography, not time of commencement of T therapy. The highlighted studies addressed in this paper can be used to guide the clinician in how to best monitor patients on TRT, especially those with the comorbid conditions detailed below. The estimated likelihood of adverse effects of long-term TRT is still essentially unknown, as overall high-quality evidence to recommend against its use in most men with TD is lacking. There is extensive evidence that human seminal Zn has an important role in the physiologic sperm functions and Zn reduced levels led to low quality of sperm and reduced fertilization chances. Zn ions can increase male fertility by regulation of the expression of testis GC-specific genes during the differentiation process and spermatogenesis (35, 36). Evidence suggests that seminal Zn has an important role in the physiologic functions of the sperm and that its reduced levels result in low seminal quality and subsequent chances of fertilization (6). However, quantity is not quality and currently, despite numerous publications it is very difficult to conclude how testosterone affects cognitions and emotions. These effects are called non-genomic and are studied for all steroid hormones. Without genetic or pharmacologic manipulation it is not possible to distinguish the effects when testosterone itself is administered. These include genetic polymorphisms related to testosterone metabolism or other pathways related to cognitive functioning (Panizzon et al., 2014). Restoring natural circulating hormone pattern in older but also in younger animals could possibly lead also to more comprehensive results of sex hormones and behavior studies. The study assessed whether rosuvastatin would have an effect on prepubertal males, to measure the safety of giving the drug to children with dyslipidemia. The limitation of the study is that the reproductive parameters were not measured before starting the study. The gonadal function was measured by evaluating the basal levels of FSH, LH, prolactin, and progesterone. Moreover, patients on clomiphene treatment did not show increases in hemoglobin, PSA, or cholesterol levels . In another study, ten male patients with idiopathic hypogonadotropic hypogonadism (IHH) received anastrozole (1 mg/d orally) . Three weeks into anastrozole treatment, the testosterone and bioavailable testosterone levels improved from 258.4 ng/dL and 128.8 ng/dL to 509.2 ng/dL and 297.5 ng/dL, respectively, while the estradiol levels decreased from 40.8 pg/mL to 24.6 pg/mL. Ever since that study, testosterone has undergone extensive clinical trials as a hormonal method of male contraception and many have found testosterone to be efficacious, reversible and safe with minimal short-term side effects . It acts synergistically with testosterone to increase fertility and the efficiency of spermatogenesis . As testosterone levels increase, negative feedback suppression is exerted on the androgen receptors in the hypothalamic neurons and pituitary gland, thereby inhibiting the release of GnRH, FSH and LH . Suppression of follicle stimulating hormone (FSH) release from the pituitary gland impairs sperm production and suppression of luteinizing hormone (LH) release inhibits intra-testicular testosterone production. So what options exist for those patients who are hypogonadal and require TST for symptomatic relief? Exogenous testosterone use, therefore, results in both impaired endocrine regulation of GnRH and LH release and subsequent decrease of endogenous testosterone. GnRH leads to the release of LH from the anterior pituitary, which then stimulates the Leydig cells in the testicles to produce testosterone. Higher cortical centers in the brain signal the hypothalamus, which in turn modulates the anterior pituitary via pulsatile secretion of gonadotropin-releasing hormone (GnRH). Do we have the ability to treat this patient's low testosterone safely and effectively? Interestingly, estradiol levels were significantly lower while using the nasal gel compared with the long-acting TRT treatments. FSH and LH levels remained similar from baseline to 1 month after conversion to the nasal gel treatment. The semen parameters (i.e., semen volume, sperm concentration, sperm total motility percentage, and forward progressive motility percentage) did not significantly change between the CC and nasal gel treatment groups. The testosterone metabolite, dihydrotestosterone, which cannot be metabolized to estradiol did not showed this effect (Bimonte-Nelson et al., 2003). In aged rats, an important experiment showed that the positive effect was found only when testosterone was administered. The organizational effect of testosterone on the hippocampus, the major memory structure in the brain has been described a long time ago in rats using various mazes (Roof and Havens, 1992; Roof, 1993). Animal experiments help us to uncover the molecular and physiological mechanisms behind the phenotype correlations seen in human studies. For health care providers, it underscores the need for a nuanced approach to treating patients who have a history of AAS use. In the current review, we found that the motivating factors for starting AAS were muscle development, increased libido, improved sexual performance, virility and alleviated ageing process. Non-uniform study population, observational nature of the studies included in our review and variable duration, type and dose of the AAS use may be a plausible reason for these findings. In our review, we included studies with male subjects taking supraphysiologic doses of AAS. This issue was addressed in a recent systematic review and meta-analysis published by Corona et al. wherein the authors included studies with male participants and most studies with supraphysiologic doses and few with therapeutic doses. For severely symptomatic patients, a 4-week tapered course of transdermal or injectable testosterone replacement therapy may provide immediate symptom improvement. Of 1549 healthy eugonadal men who participated in 30 different clinical trials, after cessation of medication, 67% showed a return to sperm concentrations above 160 million/ml within 6 months, 90% within 12 months, 96% within 16 months and 100% within 24 months. As there are no systematic investigations of the effects of doping with high-dose AAS on testicular function, contraceptive trials may serve as a model for what happens under AAS suppression. Through the hormone parameters recover by 3 months, spermatogenesis recovery is expected after 1 year. 1. Effects of oxidative stress on Zn levels of seminal plasma: Testosterone can be measured by a simple blood test and are usually measured in the morning, since that is when levels are highest in men. Testosterone (also referred to as “T”) is a hormone produced in men by the testicles. Contact Fertility Answers to make a plan for addressing hormonal imbalances while boosting fertility. Ongoing, long-term steroid use can cause other health issues — some of which may be irreversible — such as adult acne, breast development, liver problems, heart attack and stroke. Steroid use can actually lead to low (or absent) sperm counts and shrunken testicles. The testosterone patch was shown to be an ineffective contraceptive while the gel had mixed results 42,43. In terms of the contraceptive effect of the different formulations of testosterone, most research has shown that transdermal and intramuscular testosterone seem to be the strongest contraceptive formulations. It is particularly helpful in patients who travel regularly, and the extended release decreases the ‘up and down’ feelings often experienced with the intramuscular injections. Effect of omega-3 and omega-6 polyunsaturated fatty acid enriched diet on plasma IFG-1 and testosterone concentration, puberty and semen quality in male buffalo. Comparative effects of zinc oxide, zinc oxide nanoparticle and zinc-methionine on hatchability and reproductive variables in male Japanese quail. Dietary supplementation with linseed oil improves semen quality, reproduc-tive hormone, gene and protein expression related to testosterone synthesis in aging layer breeder roosters. Effects of branched-chain amino acid supplementation and/or aerobic exercise on mouse sperm quality and testosterone production. Ameliorative effects of oral ginger and/or thyme aqueous extracts on productive and reproductive performance of V-line male rabbits. Furthermore, folates play a central role in spermatogenesis with a significant increase in total normal sperm count and a minor increase of abnormal spermatozoa in double-blind, randomized, placebo-controlled trial sub-fertile and fertile men (Table 1) . In fact, the presence of omega-3 alpha-linolenic acid (ALA) is crucial for some cellular functions such as phagocytosis of residual bodies by Sertoli cells, morphology, and fluidity of the sperm membrane . Interestingly, some human studies have shown that antioxidant supplementation can reduce the oxidative stress in spermatozoa 43, 44. Likewise, in the study of Braga et al., red meat consumption was inversely related to implantation and pregnancy rate in couples undergoing intracytoplasmic sperm injection (ICSI) . Radhakrishnakartha H, Appu AP, Madambath I. Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs. Protective effect of ascorbic acid against ethanol-induced reproductive toxicity in male guinea pigs. Selenium-enriched probiotics improves murine male fertility compromised by high fat diet. Protective effects of l-arginine against testosterone synthesis decreased by T-2 toxin in mouse Leydig cells. 3. The role of Zn in cell death: Analysis of FSH showed a statistically significant increase in the hormone after statin use. There was a decrease in Free Testosterone in the cross-sectional study, but no statistical difference was seen in prospective studies, as there was an important decrease in the number of studies that analyzed the variable. Therefore, it is possible to affirm that the statin use causes a decrease in the total levels of testosterone. Total Testosterone was seen to decrease its mean at all levels of evidence, with the exception of the comparison between groups in the prospective studies. Interestingly, the addition of HMG did not significantly improve testicular volume . HCG dosages for infertile patients usually range from 3000 to 10,000 IU, 2–3 times per week . No major changes in testosterone (413 ng/dL to 433 ng/dL), FSH (3.1 to 3.05 mIU/mL), PSA (1.35 to 1.53 ng/mL), HCT (42.85 to 44.85%), estradiol (27.5 to 32 pg/mL), A1c (5.85 to 5.95%), or LH (4.8 to 4.0 mIU/mL) were observed . These methods focus on triggering endogenous testosterone production in the testes, rather than directly administering exogenous testosterone. This effect might be mediated by the organizational effect of testosterone on brain structures such as amygdala or hippocampus (Ackermann et al., 2012). Similarly to other behavioral measures memory will be influenced also by prenatal concentrations of testosterone (Bull et al., 2010). It seems that the effect of testosterone is dose-dependent and could be curvilinear even within sexes. Read real-life stories from patients who have faced reproductive medicine challenges and come out stronger on the other side. One way that ASRM works to improve access to fertility care is by advocating for insurance coverage for reproductive medicine care. ASRM's Frequently Asked Questions (FAQ) provides answers to common questions about reproductive health. SRS, an ASRM affiliate, advocates evidence-based reproductive surgery and full-spectrum fertility care for conditions like endometriosis, fibroids, and PCOS. 7 A study of steroid-using bodybuilders found that less than 18% of men with a history of using steroids had any morphologically normal sperm. They are crucial for the production of healthy sperm. However, anabolic drugs can have a negative impact on male fertility. Let’s take a look at these supplements and understand their effects on fertility. In a cohort study by Hakonsen et al., 43 men were observed over 14 weeks while they were enrolled in a residential weight loss program . Both studies reported overall improved glycemic control in participants receiving liraglutide 58,59. Participants were assigned to receive either liraglutide (3.0 mg daily) or TRT in the form of daily transdermal gel, with a short-term treatment duration of 16 weeks. Furthermore, erectile function was significantly improved in Group B, compared to Groups A and C . AIs are mainly used to control elevated estradiol (E2) levels to prevent adverse effects in men on testosterone replacement therapy. Serum testosterone levels should be closely monitored since the addition of a SERM can increase testosterone even more. However, HCG alone probably triggers similar increases in serum testosterone levels. One study investigated whether normal FSH levels are required to trigger spermatogenesis after chronic gonadotropin and testicular suppression . One study recruited 29 men with normal reproductive function and administered 200 mg/week of testosterone enanthate in addition to either a saline placebo or 125, 250, or 500 IU of HCG every other day for 3 weeks . However, they are all based on expert opinion or consensus rather than evidence provided by carefully designed studies 10, 22, 37, 62. After initiation of puberty, T doses are gradually increased to mimic normal pubertal physiology over the course of 2 to 3 years until puberty is clinically completed and adult doses are reached. No pediatric studies have been published with the most recent T formulations. Although there is encouraging evidence for the efficacy of transdermal T therapy (gels and patches), the data are limited 22, 75-77. A 2006 integrated analysis showed that 90% of patients were expected to return to baseline sperm concentration values 12 months after cessation of treatment and 100% after 24 months . Considering that there is abundant evidence demonstrating that TRT significantly decreases sperm production, it is important that clinicians consider the evidenced risks of male infertility before starting patients on TRT. With regards to fertility, Conners et al found that 4.5% NTG two or three times a day restored serum testosterone levels while only decreasing gonadotropin levels minimally, keeping serum FSH and LH values within the normal range. These two studies found an azoospermia rate of 64% to 75% in 6 months with testosterone enanthate 6,7. Partial ameliorative effect of moringa leaf ethanolic extract on the reproductive toxicity and the expression of steroidogenic genes induced by subchronic cadmium in male rats. Semen quality, antioxidant status and reproductive performance of rabbits bucks fed milk thistle seeds and rosemary leaves. Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin administration alters semen quality in healthy men. Bahrami N, Goudarzi M, Hosseinzadeh A, Sabbagh S, Reiter RJ, Mehrzadi S. Evaluating the protective effects of melatonin on di(2-ethylhexyl) phthalate-induced testicular injury in adult mice. In particular, lower T levels showed the weakest association with severe ED, which is better explained by an older age or by a higher morbidity index (Fig. 1, upper panels). The left columns show (Fig. 1, Panels A,D,G,L) the association between symptom severity and T levels, the middle columns (Fig. 1, Panels B,E,H,M) show associations with age, and the right columns (Fig. 1, Panels C,F,I,N) association with morbidities as assessed by Chronic Disease Score (CDS), an aggregate comorbidity measure based on current medication use . Data are derived from published series concerning almost 3500 patients 16, 50. Clinical data were derived from a consecutive series of 3500 patients seeking medical care at the University of Florence as previously described (see also Table 1 ). Late onset hypogonadism (LOH) is the most frequently used term to describe the latter phenomenon . The aim of this review is to analyze the molecular effects of single nutrients on sperm quality, focusing on their involvement in biochemical mechanisms related to sperm bioenergetics. A systematic review and evidence-based analysis of ingredients in popular male testosterone and erectile dysfunction supplements. The objective was to study available evidence for ingredients of popular over-the-counter testosterone and erectile dysfunction (ED) supplements. The Kolmogorov-Smirnov test was used to study the normal distribution of the studied parameters. Glutathione levels (GSH) were determined by kits obtained from Bio Diagnostic, Egypt, according to the manufacturer’s instructions. Thiobarbituric acid reactive substances (TBARS) were measured in testicular homogenates as described by Tappel and Zalkin33. These reported adverse effects on male reproductive parameters are not generally agreed upon, hence, making the aftermath effect of statin use on male fertility debatable and controversial. Not only have the use of statins caused the aforementioned side effects, but they have also been shown to cause testicular discomfort, erectile dysfunction, altered semen parameters, and modified steroid hormone production. Although some studies demonstrate that statins may have serious adverse effects on male fertility, several others showed no effect. To date, reports from both human and animal studies have remained contradictory, as there is evidence demonstrating both the lack of consequences and adverse effects of statins on male fertility. Nevertheless, it is not that simple, because testosterone, which is required for the entire process of spermatogenesis, is a steroid hormone and requires cholesterol as a precursor, but statins lower cholesterol levels. Hosseinzadeh Colgar et al. showed that, seminal Zn had a significant positive correlation with sperm count and normal morphology in fertile and infertile men (6). Zhao and Xiong observed a lower content of Zn in the seminal plasma of infertile subjects and a positive relationship with poor sperm production and poor sperm motility (44). Furthermore, it was indicated that oligospermic men with sperm counts 41). Ultimately, the low intra-testicular testosterone results in decreased proliferation of spermatogonia, defects in spermiation of mature spermatozoa by Sertoli cells and accelerated apoptosis of spermatozoa 8,9,10,11. Intra-testicular testosterone is required in spermatogenesis for the formation of the blood-testis barrier (BTB). The exogenous administration of testosterone suppresses the release of gonadotropins (FSH and LH) to levels below that required for spermatogenesis. The use of testosterone replacement therapy (TRT) among men over the age of 40 years has increased more than 3-fold over the last decade . Exogenous testosterone therapy can negatively affect the hypothalamic-pituitary gonadal axis and inhibit the production of follicle stimulating hormone and luteinizing hormone. The combination of elevated lipid peroxidation (TBARS) and depleted antioxidant systems indicates excessive mitochondrial ROS production, which can damage mitochondrial membranes and mtDNA, further lowering ATP generation and exacerbating sperm functional impairment67. During spermatogenesis and in mature spermatozoa, mitochondria localized in the midpiece are the primary source of ATP required for flagellar movement, so disturbances in mitochondrial biogenesis and function are tightly linked to reduced sperm motility and abnormal morphology66. Inflammation in the male reproductive tract activates immune cells, as confirmed by histological findings, which in turn exacerbate oxidative stress through the burst of excess ROS generation. Well, here's a wake-up call for you – those supplements might harm your fertility. While taking testosterone may not mean you become completely infertile, this is not an impossibility, especially with long-term use. This could generate a problem among men who take over-the-counter testosterone boosters who may not have low testosterone at all. However, taking testosterone may not actually mean a man is more fertile. Nevertheless, both risks can be carefully monitored as long as the patient is consistent with seeing their doctor during treatment and receives adequate periodic testing. In a study by Buckley et al. 6.6% of high school seniors reported that they used, or had a history of using, anabolic steroids.5 Unfortunately, use of exogenous testosterone is not limited to medical therapies alone as use of testosterone, and other anabolic steroids is quite common among young athletes. The latest content about treatment options, success rates, and support options. For more information, contact the fertility experts at MCRM Fertility, and visit MCRMfertility.com. The patient's desire for fertility must be discussed in depth and established prior to initiating testosterone. A list of the available testosterone formulations with its side effect profiles and effect on fertility can be found in Table 1 3,14,15,25,28,41,42,43,44,45,46,47,48. Based on what is found by future studies, NTGs may have the potential to be a suitable TRT option in men desiring fertility. Its short half-life results in a return of serum testosterone to near baseline levels between doses. The selection of the preparation of testosterone requires a comprehensive discussion with the patient about the route of administration, cost and side effects of the individual formulations. Therefore, not only TRT patients but also AAS users might face similar side effects related to male infertility. As exogenous testosterone administration increases serum testosterone levels, the amount of estrogen also increases since a part of the exogenous testosterone is converted into estrogen via the aromatase enzyme. Depending on the serum testosterone level, the HPG axis will release adequate amounts of GnRH to maintain serum testosterone levels and sperm production in balance in a self-regulating manner. Exogenous testosterone administration can lead to dramatic increases in serum testosterone levels.