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Effects of Chronic Testosterone Administration in Normal Men: Safety and Efficacy of High Dosage Testosterone and Parallel Dose-Dependent Suppression of Luteinizing Hormone, Follicle-Stimulating Hormone, and Sperm Production*
Abstract
In normal men, chronic testosterone (T) administration results in negative feedback suppression of gonadotropin and sperm production. However, azoospermia is achieved in only 50-70% of men treated with high dosages of T. Furthermore, the relative sensitivity of LH and FSH secretion to chronic administration of more physiological dosages of T is unclear. We determined whether a T dosage higher than those previously given would be more or less effective in suppressing spermatogenesis and whether, within the physiological range, T would exert a more selective effect on LH than on FSH secretion. After a 4- to 6-month control period, 51 normal men were randomly assigned to treatment groups (n = 9-12/group) receiving either sesame oil (1 mL) or T enanthate (25, 50, 100, or 300 mg, im) weekly for 6 months. Monthly LH and FSH levels by RIA and twice monthly sperm counts were determined. During treatment, T levels were measured daily between two weekly injections. Chronic T administration in physiological to moderately supraphysiological dosages resulted in parallel dose-dependent suppression of LH, FSH, and sperm production. T enanthate (50 mg/week) suppressed LH and FSH levels and sperm counts to 50% of those in placebo-treated men (ED50). T enanthate (300 mg/week), was no more effective than 100 mg/week in suppressing LH, FSH, and sperm production. Serum T levels in men who received 100 and 300 mg/week T enanthate were 1.5- and 3-fold higher than those in placebo-treated men, respectively. Except for mild truncal acne, weight gain, and increases in hematocrit, we detected no significant adverse health effects of chronic high dosage T administration. We conclude that 1) LH and FSH secretion are equally sensitive to the long term negative feedback effects of T administration; 2) sperm production is suppressed in parallel with the LH and FSH reductions induced by chronic T administration; and 3) even at the clearly supraphysiological dosage of 300 mg/week, T enanthate does not reliably induce azoospermia in normal men. However, there was also no evidence of a stimulatory effect of this T dosage on spermatogenesis. Furthermore, we found no evidence of major adverse health effects of T administered chronically even at the highest dosage.
... Unfortunately, due to a lack of accurate data in the literature, it is currently not possible to estimate the prevalence of azoospermia, oligozoospermia, and severe oligospermia in male AAS users; however, studies on male contraceptive therapies may shed some light on the efficacy of testosterone intake and reduced sperm count. Briefly, the study of male infertility has been dated from the early 1990s, when Matsumoto (1990) reported that 6 months of supraphysiological doses of testosterone (i.e., ≥100 mg per week) drastically suppressed sperm counts. That study also revealed that even smaller doses of testosterone (i.e., 25 and 50 mg per week) also negatively affected sperm counts in young males (Matsumoto, 1990). ...
... Briefly, the study of male infertility has been dated from the early 1990s, when Matsumoto (1990) reported that 6 months of supraphysiological doses of testosterone (i.e., ≥100 mg per week) drastically suppressed sperm counts. That study also revealed that even smaller doses of testosterone (i.e., 25 and 50 mg per week) also negatively affected sperm counts in young males (Matsumoto, 1990). More recently, studies on male contraception therapies showed a high impact of exogenous testosterone doses on reducing sperm counts (Gu et al., 2009;Gu et al., 2003), as one study found~95% of treatment efficacy in inducing azoospermia or severe oligozoospermia within the 6month treatment period (Gu et al., 2009). ...
... A recent narrative review, which utilized data from five controlled randomized trials, provided an estimated time course of male infertility according to the type and dose of testosterone utilized, in which the time to reach azoospermia or oligospermia varied between 90 and 180 days, respectively. Specifically, whereas one study exhibited reduced sperm counts within 90 days following the use of AAS (i.e., 200 mg enanthate weekly doses) (World Health Organization, 1996), another study found reduced sperm counts within 180 days (i.e., 100-300 mg enanthate weekly doses) (Matsumoto, 1990). Thus, exogenous testosterone could be highly effective to induce and maintain male infertility. ...
The evolving prevalence of anabolic androgenic steroids (AAS) abuse among nonathletes is alarming because of the known harm to an individual’s health. Among the adverse effects of AAS abuse, male infertility and sexual dysfunction have been often reported in the literature, but little is known regarding its actual prevalence, possible underpinning mechanisms, and potential treatments either during or post-AAS usage. Thus, the current narrative review summarizes the state-of-art regarding the effects of AAS on male fertility and sexual function. Evidence was gathered from the latest reviews and recent original studies, specifically from prospective cohorts and clinical trials, ultimately resulting in five main topics of discussion. First, AAS usage is briefly characterized by its historical background, main physiological mechanisms, and the most frequently used AAS substances. Second, data on the prevalence of AAS-induced male infertility and sexual dysfunction are described. Third, some new insights on possible underpinning mechanisms of AAS-induced male infertility and sexual dysfunction are thoroughly discussed, with particular attention to histological data derived from animal models and the latest insights from prospective cohorts in humans. Fourth, the potential treatments during and after the AAS usage are presented, highlighting the odds of resolving male infertility and sexual dysfunction. Fifth, future directions on this topic are discussed, focusing on the methodological robustness of scientific studies.
... One study looking at the effects of different dosages of testosterone enanthate (25, 50, 100, or 300 mg) weekly for 6 months showed that administration of testosterone enanthate to healthy men led to a significant dose-dependent parallel suppression of serum LH and FSH levels [16]. Serum LH and FSH levels were 101 ± 6% and 102 ± 3% of the control values in men in the sesame oil injection group and 91 ± 7% and 97 ± 4% of the control values in the 25 mg testosterone enanthate group, respectively. ...
... An amount of 50 mg weekly led to severe suppression of both LH and FSH levels to 65 ± 8% and 62 ± 7% of the control values, respectively. LH and FSH levels were downregulated to 32 ± 2% and 34 ± 5% in the 100 mg weekly group and 31 ± 3% and 29 ± 3% in the 300 mg weekly group, respectively [16]. Sesame oil (placebo) injections led to a reduction in sperm counts to 72 ± 7% of the control values. ...
... An amount of 50 mg per week downregulated sperm counts to 36 ± 8% compared with the control values. An amount of 100 or 300 mg per week downregulated sperm counts to 0.8 ± 0.4% and 3 ± 2% compared with the control values [16]. ...
Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic–pituitary–gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.
... 43 -45 In 1990, Matsumoto et al. revealed supraphysiological T regimens (ie, ≥ 100 mg weekly) maximally suppress sperm count. 45 Healthy men were divided into 5 groups: one receiving placebo and the others receiving T enanthate at 25, 50, 100, and 300 mg weekly for 6 months. 45 While T at 25 and 50 mg partially suppressed sperm count, 100 and 300 mg maximally suppressed the spermatogenesis in the subjects leading to severe oligospermia or azoospermia. ...
... 45 Healthy men were divided into 5 groups: one receiving placebo and the others receiving T enanthate at 25, 50, 100, and 300 mg weekly for 6 months. 45 While T at 25 and 50 mg partially suppressed sperm count, 100 and 300 mg maximally suppressed the spermatogenesis in the subjects leading to severe oligospermia or azoospermia. 45 Two studies by the World Health Organization Task Force on Methods for the Regulation of Male Fertility, published in 1990 and 1996, evaluated the use of 200 mg of intramuscular T enanthate for male contraception in previously eugonadal men and the average time to occurrence of severe oligospermia or azoospermia was 91 to 120 days. ...
... 45 While T at 25 and 50 mg partially suppressed sperm count, 100 and 300 mg maximally suppressed the spermatogenesis in the subjects leading to severe oligospermia or azoospermia. 45 Two studies by the World Health Organization Task Force on Methods for the Regulation of Male Fertility, published in 1990 and 1996, evaluated the use of 200 mg of intramuscular T enanthate for male contraception in previously eugonadal men and the average time to occurrence of severe oligospermia or azoospermia was 91 to 120 days. 43 , 44 In the 1990 WHO study, more than 70% of the patients developed azoospermia in the hormone suppression phase, and those who did not become azoospermic had severe oligozoospermia. ...
Purpose
To review the impact of testosterone and other androgenic-anabolic steroids (AASs) on male fertility, exploring potential drugs that can be used to preserve or restore male fertility upon AAS use or prior contact.
Methods
A review was performed to provide a unifying clinical link between drugs used to preserve or restore male fertility (ie, clomiphene citrate, human chorionic gonadotropin, selective estrogen receptor modulators, recombinant luteinizing and follicle-stimulating hormones, and human menopausal gonadotrophin) in the context of AAS-induced infertility and related aspects.
Findings
Human chorionic gonadotropin (125–500 IU every other day), clomiphene citrate (12.5–50 mg/d), recombinant luteinizing hormone (125–500 IU every other day), recombinant follicle-stimulating hormone (75–150 IU 1–3×/wk), and human menopausal gonadotrophin (75–150 IU 1–3×/wk) are promising early pharmacologic approaches to avert AAS-induced male infertility. Additionally, a full partner assessment is crucial to the success of a couple planning to have children. The partner's age and gynecopathies must be considered. Egg or sperm cryopreservation can also be alternatives for future fertility. Reinforcing AAS cessation is imperative to achieving better success in misusers.
Implications
The exponential increase in AAS misuse raises concerns about the impact on male fertility. This review suggests that gonadotropin analogs and selective androgen receptor modulators (clomiphene citrate) are viable approaches to early preserve or restore fertility in men on AAS use or with previous contact. However, proper standardization of doses and combinations is required and hence physicians should also be aware of patients’ and partners’ fertility.
... Furthermore, treatment of male hypogonadism with testosterone resulted in the suppression of the elevated LH and FSH concentrations to normal [30] . In normal men, chronic testosterone administration resulted in negative feedback suppression of FSH and LH and sperm production and this effect was found to be dose dependent [31] . Dose-related depression of both LH and FSH was also observed in adult males subsequent to administration of 5 mg or more of testosterone per day [32] . ...
... In normal men, chronic testosterone administration results in negative feedback suppression of gonadotropin and sperm production [37] . However, azoospermia is achieved in only 50-70 % of men treated with high dosages of testosterone [31] . Testosterone inhibits gonadotropin-releasing hormone (GnRH) and gonadotropin secretion. ...
Testosterone (T) is a hormone has been abused by some athletes to increase muscle mass and to tolerate stress and exhaustion from hard exercises; and it has also been used by older men for rejuvenation. However, there are not many studies on animals investigating the side effects of this hormone with high doses. Therefore, the aim of this work was to investigate the effects of two different doses of testosterone on the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and the histology of the testes of rabbits. Fifteen Egyptian male rabbits were weighed and divided into 3 groups: 1- Control group (received 100 μl sesame oil), 2- Low dose group (received 6 mg testosterone/kg b. w.), and 3- High dose group (received 12 mg testosterone/kg b. w.). The rabbits were injected with testosterone intramuscularly once a week for 6 weeks. After the end of the treatment period, the rabbits were slaughtered, blood samples were taken for hormonal analysis, and testes were dissected out, weighed and kept in a fixative for histological analysis. Injection of the rabbits with T resulted in a significant increase in the level of this hormone in the serum of treated animals in comparison with the control group. Testosterone at both doses significantly reduced the level of FSH but had no significant effect on the level of LH. The mean weights of the treated testes did not differ significantly from that of the control group. Cross sections from the testosterone treated testes showed large spaces between the seminiferous tubules and reduced spermatogenesis. It is concluded that T has significant effect on the reproductive hormones and the testicular tissue, which could cause on the long run infertility.
... Testosterone enanthate is the most widely used replacement androgen [3,4]. While the clinical effectiveness and safety is well established, it has the disadvantage of requiring i.m. or s.c. ...
... While the clinical effectiveness and safety is well established, it has the disadvantage of requiring i.m. or s.c. administration at 1 to 3 week intervals [3,5]. Testosterone cypionate must also be injected at similar intervals [6]. ...
... Most of these side effects are dose-dependent, with the most common being increased blood pressure, especially in those with pre-existing hypertension. [19] Steroids have been shown to alter blood sugar tests. [20][21] ...
The current study aimed to reveal the cytogenetic effects of Methandienone in white mice Mus Musculus, which is widely used in gyms, by studying some blood images through tests by choosing a third of the dose (0.8) mg/kg of the body weight of the laboratory mouse. The results showed that the increase in the drug has the ability to produce _____ white blood cells and ___ red blood cells at an equal rate. In conclusion, the results of this study show that the drug has mutagenic effects.
... The biological efficacy of these drugs is demonstrated by muscle mass increase, growth spurts in premature children, and bone loss attenuation in older adults [6,7], These compounds are prescribed for various therapeutic purposes. However, long-term or excessive usage may cause side effects, such as skin diseases [7] or reproductive and endocrine functional deterioration [8,9]. Aiming to treat impaired myogenesis via metabolic changes, Belli et al. reported that trimetazidine, a metabolic modulator drug, may induce myoblast differentiation in a cell line and increase muscle strength in mice [10]. ...
Growth and maintenance of skeletal muscle is essential for athletic performance and a healthy life. Stimulating the proliferation and differentiation of muscle cells may help prevent loss of muscle mass. To discover effective natural substances enabling to mitigate muscle loss without side effects, we evaluated muscle growth with several compounds extracted from Catalpa bignonioides Walt. Among these compounds, pinoresinol and vanillic acid increased C2C12, a mouse myoblast cell line, proliferation being the most without cytotoxicity. These substances activated the Akt/mammalian target of the rapamycin (mTOR) pathway, which positively regulates the proliferation of muscle cells. In addition, the results of in silico molecular docking study showed that they may bind to the active site of insulin-like growth factor 1 receptor (IGF-1R), which is an upstream of the Akt/mTOR pathway, indicating that both pinoresinol and vanillic acid stimulate myoblast proliferation through direct interaction with IGF-1R. These results suggest that pinoresinol and vanillic acid may be a natural supplement to improve the proliferation of skeletal muscle via IGF-1R/Akt/mTOR signaling and thus strengthen muscles.
... Due to suggestion of other studies (32)(33)(34), sperm concentration decreased by damage of germ cell and shedding immature spermatid in epididymis and seminiferous tubule or directly attaching of gossypol to membrane of seminiferous tubule and following by facilitating the cell destruction through increase fragility of membrane in the testis. However, the other research stated that a decrease in the sperm concentration is due to a decrease in the serum testosterone (35). Depletion of spermatogenic cell in seminiferous tubule, histopathology investigation shows main toxicity effect of gossypol that previously reported (36). ...
Effects of cottonseed flour in male and female rats’ fertility based on hormonal and histomorphometry changes were studied. Sixty-four Sprague-Dawley adult male and female rats were randomly divided into control and treatment groups. Treatment group was received diets containing cottonseed flour for 35 days. Control group was given standard rat food. Body and testis weights, epididymis semen evaluation indices and serum sex steroid hormones were determined. Histomorphometry alterations of testes and ovary were evaluated. Then, normal female and male rats were mated by rats in both groups and after 35 days, number of pups was measured. However, there was no significant difference in whole body and testes weights, sperm concentration and viability between the control and treatment groups, respectively. Moreover, sperm motility in the treatment rats was significantly lower than the control group. Serum hormones alterations were not significant, but histomorphometry evaluations of testes showed significant changes in the testis structures after chronic consumption of cottonseed flour. In the female rats, body weight did not have significant difference between the treatment and control groups. Histomorphometry data in female ovary showed significant reduction of primary follicle volume and number in the treatment group against control. Follicle stimulating hormone showed insignificant reduction in the treatment group. Number of pups was significantly reduced in the female rats fed by cottonseed flour. Cottonseed flour in rat diet had adverse effects on rat reproduction. Therefore, it can be used as an efficient product for control of the rat population as a natural rodenticide agent.
... n.d.: no data; SEM: standard error of the mean males. The mechanism could be the negative feedback of T on gonadotropin releasing hormone similar to the feedback mechanism observed in mammals during prolonged T elevation (Matsumoto, 1990; reviewed in Melmed, 2016 andRoth, Page, &Bremner, 2016). ...
In brown kiwi (Apteryx mantelli), the male is the primary incubator, a trait that is relatively rare among birds. The maintenance of avian incubation behavior is controlled by the protein hormone prolactin (PRL). Although steroid hormone concentrations in both wild and captive kiwi have previously been reported, this study is the first to report levels of PRL in captive and wild male and female kiwi through the prebreeding and breeding seasons, and to directly compare testosterone (T) concentrations between captive and wild males during the breeding and incubation periods. Female PRL concentrations increased at the time of oviposition, whereas male PRL concentrations rose gradually between the prebreeding and incubation periods. Although males are considered the main incubator, an increase in PRL levels could help females maintain behaviors such as nest guarding, or to take over incubation the event of mate loss. A gradual increase in PRL allows the male to be ready for incubation during the long breeding season. Interestingly, T concentrations in captive males did not decrease during incubation and was significantly higher than in wild males. Continual elevated T could have an impact on sperm production through negative feedback, thereby contributing to the low egg fertility seen in captive kiwi. Therefore, determining the underlying reason for the differences in hormone levels could be significant, if not vital, for improving the success of captive kiwi breeding programs.
... The hypothalamus and the pituitary gland are the primary regulators of the intratesticular microenvironment through negative feedback of T (2,10). Exogenous T administration at both physiologic and supraphysiologic doses can dramatically suppress gonadotropin release (11,12). This can lead to a decrease in sperm in 65% of men to levels sufficient for contraception (13,14). ...
Serum testosterone values vary considerably with little correlation to intratesticular testosterone (ITT). ITT is approximately ~100 times that of serum testosterone and is critical for spermatogenesis. Unfortunately, the only method to accurately measure ITT is invasive testicular aspiration and therefore is not performed routinely. The identification of a serum biomarker for ITT would allow serial monitoring during hormonal manipulation and the ability to assess the effectiveness of a male contraceptive agent. Prior studies have evaluated several serum biomarkers for their ability to accurately reflect ITT with data supporting 17-hydroxyprogesterone (17-OHP) and insulin-like factor 3 (INSL3) as a potential marker. Because evaluation of serum 17-OHP is readily available through commercial laboratories, in this review, we present the evidence for 17-OHP and how it can play a pivotal role in the management of male infertility.
... Numerous studies have shown that long-term use or excessive dosing of anabolic steroids can lead to serious health risks. One physiologic change is a dose-dependent impairment of normal testicular androgen secretion and spermatogenesis [7][8][9] . This effect is believed to result from the suppression of circulating luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a feedback loop system of the hypothalamic-pituitary-gonadal (HPG) axis 9,10 . ...
A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate. Thirty-one healthy males were randomized into a dose group of 100, 250 or 500mg/wk and received 14 weekly injections of TC. A PK-PD model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration. A linear one-compartment model best described the concentration-time profile of total testosterone. The population mean estimates for testosterone were 2.6 kL/day for clearance and 14.4 kL for volume of distribution. Weight, albumin and their changes from baseline were identified as significant covariates for testosterone. The estimated potency of total testosterone with respect to suppression of LH synthesis was 9.33 ng/ml. Simulation based on the indirect response model suggests the suppression of endogenous testosterone secretion, LH synthesis and spermatogenesis was more severe and of greater duration in 250mg and 500mg dose groups. This article is protected by copyright. All rights reserved.
... However, the other androgenic pathway of action is via rebound effect (e.g. testosterone enanthate) through the suppression of both spermatoge-nesis and gonadotrophins (follicle stimulating hormone and luteinizing hormone) secretion (Anonymous, 1990;Jockenhovel et al., 1999;Matsumoto, 1990;Van dekerckhove et al., 2000). Thus, there is usually reversal of these androgen-induced symptoms when such drugs are discontinued in some cases. ...
Anabolic-androgenic steroid compounds are one of the most widely abused drugs by athletes and muscle builders with the goal of improving performance/muscle mass. However, increasing concern has been expressed because these compounds not only offer unappreciable benefits to infertile and subfertile males, but also might have deleterious effects on both human and animal physiology including sperm quality. In addition, there is the conflicting outcome of AAS usage in the clinical settings with its attendant reduced spermatogenesis and hypopituitarism in patient management. Hence, we aim to evaluate the effects of mestorolone, an anabolic-androgenic steroid, on the histomorphometry of seminiferous tubules with serum hormonal and seminal analyses in adult male Sprague-Dawley rat. Twenty adult male Sprague dawley rats divided into two groups of 10 each. The treated group received 0.06 mg/g body weight/ day of mesterolone (proviron) by oral gavage for six weeks while the control group received equal volume of 0.9% normal saline per day. SPSS analysis of data generated with P< 0.05 considered statistically significant. The result showed significant (P< 0.05) body weight gain in all the animals. However, both the raw testicular weight and relative testicular weight per 100 g bwt was significantly (P< 0.05) higher in control than treated. The mean sperm count significantly decreased by 28% (P< 0.05) and the motility reduced significantly by 56% (P< 0.05) in the treated compared to control. In addition, both FSH (follicle stimulating hormone) and T (testosterone) of the treated were significantly lowered by 73% (P< 0.05) and 63% (P< 0.05) respectively compared to the control. The use of mesterolone is with caution and short intermittent therapy is desirous for better semen quality and improved overall fertility.
Keywords: Proviron, sperm parameters, germ cells, stereology, hormonal profiles, Sprague dawley rats.
... The reduction in the sperm concentration may be explained by the reduction of serum testosterone, thus impaired spermatogenesis associated with testosterone deficiency [20,21]. Results of [22] showed that the reduction of sperm concentration may related to direct binding of gossypol with spermatozoal membrane which lead to the loss of fluidity and elasticity of membrane with facilitate the cell destruction through increase fragility of membrane in the bulls. ...
Two cottonseed extracts including alcoholic and aqueous at doses 20 and 40 mg/Kg/day were orally administered to male mice for 6 weeks to study their effects on some of sperm parameters. Results showed that 20 and 40 mg/kg alcoholic and aqueous extract caused highly significant (P 0.01) decrease in the sperm concentration, motility (%) and progressive sperm motility (%). While, Results of the abnormal sperm morphology (%) for two treated groups 20 and 40 mg/kg/day of alcoholic and aqueous extracts revealed a significant (P 0.05) increase after 6 weeks when compared to the control group. Results revealed that the percentages of sperm agglutination were highly significant (P 0.01) increased in mice treated with 20 and 40 mg/kg/day of alcoholic and aqueous when compared to the control. The fertility (%) and percentage of males of new born babies showed a significant (P 0.05) reduction in the treated mice as compared to female in the same groups and to the control group. Meanwhile, a significant (P 0.05) increase in the recovery time was showed with the increasing of doses of the two extracts when compared with the control group.
... The reduction in the sperm concentration may be explained by the reduction of serum testosterone, thus impaired spermatogenesis associated with testosterone deficiency [20,21]. Results of [22] showed that the reduction of sperm concentration may related to direct binding of gossypol with spermatozoal membrane which lead to the loss of fluidity and elasticity of membrane with facilitate the cell destruction through increase fragility of membrane in the bulls. ...
Two cottonseed extracts including alcoholic and aqueous at doses 20 and 40 mg/Kg/day were orally administered to male mice for 6 weeks to study their effects on some of sperm parameters. Results showed that 20 and 40 mg/kg alcoholic and aqueous extract caused highly significant (P 0.01) decrease in the sperm concentration, motility (%) and progressive sperm motility (%). While, Results of the abnormal sperm morphology (%) for two treated groups 20 and 40 mg/kg/day of alcoholic and aqueous extracts revealed a significant (P 0.05) increase after 6 weeks when compared to the control group. Results revealed that the percentages of sperm agglutination were highly significant (P 0.01) increased in mice treated with 20 and 40 mg/kg/day of alcoholic and aqueous when compared to the control. The fertility (%) and percentage of males of new born babies showed a significant (P 0.05) reduction in the treated mice as compared to female in the same groups and to the control group. Meanwhile, a significant (P 0.05) increase in the recovery time was showed with the increasing of doses of the two extracts when compared with the control group.
... However, until now, testosterone (TS) has been chemically produced from androst-4ene-3,17-dione (AD) (Ercoli and Ruggierii, 1953). Not only being expensive, the synthetic form has been reported to induce several side-effects such as allergy, nausea or vomiting, impotency, painful or difficult urination, high levels of calcium in the blood, mild truncal acne, weight gain (Matsumoto, 1990) and coronary heart disease (Tripathy et al., 1998 ). In mammals, 17-ketoster- oid reductase (17b-HSD) enzyme catalyses the synthesis of TS from AD. ...
... In addition, most androgenic activities are either through their direct stimulatory increase in intratesticular testosterone level that in turn enhances spermatogenesis and positively influences sperm transport and maturation through its action on epididymis, ductus deferens and seminal vesicles [8], or by their rebound effect through the suppression of both spermatogenesis and gonadotrophins (follicle stimulating hormone and luteinizing hormone) secretion [8][9] [10]. ...
Tetracycline (TET) is a popular broad spectrum antibiotics known to man for treating infections mainly bacterial for many years now. However, due to paucity of knowledge; we aim to study its impact and mechanism on the male reproductive organs of treated Wister rats using histomorphometric and hormonal analysis methods. Twenty-one adult male Wister rats with average weight of 135g were divided into three groups. Two treated groups received a daily oral dose of TET at 2.0 mg/kg bwt and 4.0mg /kg bwt respectively via gastric gavage, while equal volume of normal saline was administered to the control group for five weeks. The result showed that TET administration caused a significant reduction in the testosterone level, as well as induction of adverse histo-pathologic changes in the testes. However, there was a significant increase (P<0.05) in the weights of the male accessory sex glands-(prostate and seminal vesicles) as compared to the control animals in a dose-dependent manner. Hence, we concluded that TET administration is deleterious on male accessory organs with mechanisms associated with Testosterone imbalance probably at HPT-axis level.
... Other seasonally reproductive species exhibit peak sperm production after serum testosterone peaks (Byers et aI., 1983;Asher et aI., 1987;Matsubayashi et aI., 1991). This delay may represent the observed inhibitory effects that high testosterone can have on spermatogenesis (Matsumoto, 1990;Tom et aI., 1991). Submaximal concentrations of testosterone may be required for optimum sperm recruitment. ...
‘Here in this well concealed spot, almost to be covered by a thumb nail, lies the very mainspring of primitive existence; vegetative, emotional and reproductive’.
Testosterone is the predominant androgen in men and has important physiological functions. Due to declining testosterone levels from a variety of causes, testosterone replacement therapy (TRT) is increasingly utilized, while testosterone is also abused for aesthetic and performance-enhancing purposes. It has been increasingly speculated that aside from more well-established side effects, testosterone may cause neurological damage. However, the in vitro data utilized to support such claims is limited due to the high concentrations used, lack of consideration of tissue distribution, and species differences in sensitivity to testosterone. In most cases, the concentrations studied in vitro are unlikely to be reached in the human brain. Observational data in humans concerning the potential for deleterious changes in brain structure and function are limited by their inherent design as well as significant potential confounders. More research is needed as the currently available data are limited; however, what is available provides rather weak evidence to suggest that testosterone use or abuse has neurotoxic potential in humans.
Sarcopenia is a disease in which skeletal muscle decreases with age. Stimulating the proliferation and differentiation of muscle cells may help prevent sarcopenia. To discover effective natural substances enabling to treat muscle loss without side effects, we evaluated muscle growth with several compounds extracted from Catalpa bignonioides Walt. Among these compounds, pinoresinol and vanillic acid increased C2C12, a mouse myoblast cell line, proliferation the most without cytotoxicity. These substances activated the Akt/mammalian target of rapamycin (mTOR) pathway, which positively regulates the proliferation of muscle cells. In addition, they strongly bound to insulin-like growth factor 1 receptor (IGF-1R), which is an upstream of the Akt/mTOR pathway, indicating that both pinoresinol and vanillic acid stimulate myoblast proliferation through direct interaction with IGF-1R. These results suggest that pinoresinol and vanillic acid may improve the proliferation of skeletal muscle via IGF-1R/Akt/mTOR signaling and thus alleviate diseases such as sarcopenia.
Androgenic steroids have been abused by elite athletes for decades. Their performance-enhancing properties for sports that involve strength and power have been confirmed, and this class has been banned from most elite athletic competitions since the mid-1970s. There is a risk of a withdrawal syndrome that includes severe depression, and there seems to be an increased risk of cardiovascular disease associated with chronic abuse. In contrast to high-dosage androgen abuse, androgen therapy at near-physiological dosages is generally safe and effective for male hypogonadism and potential use in sarcopenia and male hormonal contraception.
Intratesticular testosterone is vital for spermatogenesis, male fertility, and virility. Currently the only method to assess levels of intratesticular testosterone is to perform testicular biopsy which is invasive and can lead to several complications. Approaches to assess intratesticular testosterone have been understudied but hold promise as future male contraceptive agents and may grant the ability to monitor patients undergoing hormonal changes from therapeutic and diagnostic perspectives. Previous studies have sought to assess the utility of 17-hydroxyprogesterone (17-OHP) and insulin-like factor 3 (INSL3) as accurate surrogate biomarkers of intratesticular testosterone. The aim of this review is thus to highlight the importance of intratesticular testosterone and the consequent advances that have been made to elucidate the potential of biomarkers for intratesticular testosterone in the context of male infertility.
Background and Objectives
Anabolic‐androgenic steroid (AAS) use has become a major worldwide substance use disorder, affecting tens of millions of individuals. Importantly, it is now increasingly recognized that some individuals develop uncharacteristically violent or criminal behaviors when using AAS. We sought to summarize available information on this topic.
Methods
We reviewed the published literature on AAS‐induced behavioral effects and augmented this information with extensive observations from our clinical and forensic experience.
Results
It is now generally accepted that some AAS users develop uncharacteristically violent or criminal behaviors while taking these drugs. Although these behaviors may partially reflect premorbid psychopathology, sociocultural factors, or expectational effects, accumulating evidence suggests that they are also attributable to biological effects of AAS themselves. The mechanism of these effects remains speculative, but preliminary data suggest a possible role for brain regions involved in emotional reactivity, such as the amygdala and regions involved in cognitive control, including the frontal cortex. For unknown reasons, these effects appear idiosyncratic; most AAS users display few behavioral effects, but a minority develops severe effects.
Conclusion and Scientific Significance
Professionals encountering AAS users in clinical or forensic settings should be alert to the possibility of AAS‐induced violence or criminality and should employ strategies to assess whether AAS is indeed a contributory factor in a given case. Further research is needed to elucidate the mechanism of AAS‐induced violence and to explain why only a subset of AAS users appears vulnerable to these effects. (Am J Addict 2021;00:00–00)
This analysis was designed to determine the efficacy of anastrozole, an aromatase inhibitor, combined with testosterone in a subcutaneous implant in preventing elevated estradiol levels and the subsequent side effects of excess estrogen associated with testosterone therapy. It also allowed for the establishment of normative ranges of serum testosterone levels on subcutaneous implant therapy. The study participants were 344 men who were accrued to an institutional review board-approved cohort study between April 2014 and 2017. Efficacy of the subcutaneous combination implant in maintaining low estradiol levels was evaluated. Serum levels of testosterone and estradiol were measured throughout the implant cycle, at week 4, and when symptoms returned. Correlations between patient demographics, dosing, and serum levels on therapy were evaluated. Mean testosterone dose was 1827 ± 262 mg. Mean anastrozole dose was 15.3 ± 3.2 mg with the majority of men receiving 16 mg of subcutaneous anastrozole. The mean interval of insertion was 4.8 months. Low estradiol levels were maintained throughout the implant cycle. Mean T level at week 4 was 1183 ± 315 ng/dl and 553 ± 239 ng/dl when symptoms returned. Levels of testosterone on therapy inversely correlated with body mass index. There were no adverse events attributed to testosterone or anastrozole therapy. Subcutaneous anastrozole delivered simultaneously with testosterone allowed for higher dosing of testosterone and less frequent intervals of insertion. Low-dose anastrozole released from the combination implant maintained low estradiol levels throughout the implant cycle and prevented clinical side effects attributed to excess estrogen.
This analysis was designed to determine the efficacy of anastrozole, an
aromatase inhibitor, combined with testosterone in a subcutaneous implant in
preventing elevated estradiol levels and the subsequent side effects of excess
estrogen associated with testosterone therapy. It also allowed for the
establishment of normative ranges of serum testosterone levels on
subcutaneous implant therapy. The study participants were 344 men who were
accrued to an institutional review board-approved cohort study between April
2014 and 2017. Efficacy of the subcutaneous combination implant in maintaining
low estradiol levels was evaluated. Serum levels of testosterone and estradiol
were measured throughout the implant cycle, at week 4, and when symptoms
returned. Correlations between patient demographics, dosing, and serum levels
on therapy were evaluated. Mean testosterone dose was 1827 + 262 mg. Mean
anastrozole dose was 15.3 + 3.2 mg with the majority of men receiving 16 mg of
subcutaneous anastrozole. The mean interval of insertion was 4.8 months. Low
estradiol levels were maintained throughout the implant cycle. Mean T level at
week 4 was 1183 + 315 ng/dl and 553 + 239 ng/dl when symptoms returned.
Levels of testosterone on therapy inversely correlated with body mass index.
There were no adverse events attributed to testosterone or anastrozole therapy.
Subcutaneous anastrozole delivered simultaneously with testosterone allowed
for higher dosing of testosterone and less frequent intervals of insertion. Lowdose
anastrozole released from the combination implant maintained low
estradiol levels throughout the implant cycle and prevented clinical side effects
attributed to excess estrogen.
In an effort to find new and safer treatments for osteoporosis and frailty, we describe a novel series of selective androgen receptor modulators (SARMs). Using a structure-based approach, we identified compound 7, a potent AR (ARE EC50 = 0.34 nM) and selective (N/C interaction EC50 = 1206 nM) modulator. In vivo data, an AR LBD X-ray structure of 7, and further insights from modeling studies of ligand receptor interactions are also presented.
Objectives:
The aim of the present study was to investigate the association between somatic health and former abuse of AAS in former elite male athletes 30 years after the end of their active sports career.
Design:
Retrospective follow-up study.
Methods:
N=996 former elite male athletes were sent a questionnaire concerning sociodemographic variables, previous and past sport activity and lifetime prevalence of seeking professional help for health problems. N=683 (68.6%) answered the questionnaire. The lifetime prevalence of AAS-abuse was 21% (n=143), while 79% (n=540) did not admit having ever used AAS.
Results:
Former AAS-abuse was associated with tendon ruptures (p=0.01), depression (p=0.001), anxiety (p=0.01) and lower prevalence of prostate hypertrophy (p=0.01) and decreased libido (p=0.01). Former advanced AAS-abusers had higher anxiety (p=0.004) compared to the former less advanced AAS-abusers. Moreover, former advanced AAS-abusers, compared to AAS-naïves, reported more psychiatric problems (p=0.002), depression (p=0.003) and anxiety (p=0.00).
Conclusions:
A former AAS-abuse seems to be associated with some somatic and mental health problem, although a former less advanced AAS-abuse is related to lower incidence of prostate hypertrophy. The results raise the question whether some of these associations might be dose- and frequency dependent. These findings should however be seen as hypothesis generating and further studies are needed.
The present study was conducted to investigate
the effect of ( Sustanon
t
250;
abusing on reproductive efficiency .Thirty two male and thirty two female rats were
used'Theyweredividedintofourgroups(eachgroupconsistedofSmalesand8
females).Thefirstgroupservedascontrolgroupinwhichtheratsdosedby
intramuscular
injection of 10 p I olive oil weekly for !2 weeks '
the rest 3 treated
groups(Gl.G2andG3)inwhichtheratsdosedbyintramuscularinjectionof50.l00
and 150 mg Sustanon
t
250 / kg B.W. respectively
weekly for 12 weeks' then all rats
were terminated to determine testosterone ,FSH
and LH levels in addition to seminal
analysis . The results reveled that testosterone level was significantly
(pS 0'05)
elevated in Gr and G2 . The LH and FSH were significantly
decreased(ps
0.05) in all
animals .The seminal analysis in response to Sustanon
t
250 injection revealed a
significant
.
reduction in the sperm concentration,
viable spenn
percentage and
morphologicallynormalspermpercentage'Anothergroupof16maleand32female
rats were used ,to
determine the reproductive efficiency ,
from which 4 male and 8
femaleweredosedbyintramuscularinjectionwithl0ploliveoilweeklyfor12
rveeks,theyareconsideredascontrolanimalsTherestratsweredosedby
intramuscular
injection of.150 mg Sustanon
@
250 / kg B'W' weekly for 12 weeks '
Thentheyweredividedintofourgroups:groupl(4nontreatedmaleswithSnon
treated females ) ,
group 2 (4 treatedmales with 8 treated females )'
group 3 (4 treated
males with 8 non treated females) and group 4 (4 non treated males with 8 treated
females )
. After they were allowed to mate for 12 weeks ,
the reproductive
parameters
were investigated
which revealed
the fertility percentage as 100% in Gl 'whereasthfemale rats in G2 ,
G3 and
,
G4 showed no pregnancy at all which indicated complete
infertility.
Numerous publications have addressed the medical, ethical, and legal issues surrounding nonmedical hormone use by healthy individuals. The ethical and legal implications of hormone use in sports to enhance performance are clear—it is unethical and illegal. However, the medical implications surrounding this practice are far less certain, particularly when hormones are used to enhance appearance or performance in noncompetitive athletic settings. A considerable amount of misinformation exists among both users and their primary-care physicians. Many in the medical/scientific community are unaware of why some of these drugs are used, their basic mechanisms of action, and differences among agents within a class of drugs, such as anabolic-androgenic steroids. In addition, sensationalistic media coverage and anecdotal case reporting have further clouded our understanding of performance-enhancing drugs, has impeded research, and has suppressed potentially important clinical applications of these agents. Therefore, the purpose of this chapter is to
1.
Provide an overview of hormones and related drugs commonly used to enhance performance and/or physical appearance;
2.
Provide a critique of the various rationales given by individuals to support their use of performance-enhancing drugs; and
3.
Discuss the basis for the prevailing dogmas surrounding the nonmedical use of hormones, particularly those involving side effects and overall risk.
El dopaje ha causado mucho daño en el mundo del deporte y de la actividad física, rechazado por deportistas, por entrenadores y por directivos, siendo perseguido, con el fin de ser erradicado de las justas deportivas, donde su empleo es causado por la presión de innumerables factores, que se presentan en el alto rendimiento; sin embargo, se desconoce el impacto y la popularidad que muchas de estas sustancias tienen en la gente del común; quienes buscan una perfección física, desconociendo las alteraciones funcionales, fisiológicas, bioquímicas y psicológicas que, en la mayoría de los casos, son irreversibles, con el único objetivo de encajar en los patrones de belleza, que impone la sociedad. Este trabajo recopila evidencia científica sobre los efectos de la ingesta de esteroides anabólicos androgénicos en el organismo, para generar conciencia en los potenciales usuarios y crear políticas de prevención, frente al consumo indiscriminado de dichas sustancias.
//
Doping has caused much harm to the world of sport and physical activity, this has been rejected by athletes, coaches and managers, being chased to be eradicated in the just sports. However, it ignores the impact and popularity that many of these substances have in common people, who are seeking physical perfection, ignoring functional alterations, physiological, biochemical and psychological in most cases irreversible, with the sole purpose of fitting into the standards of beauty imposed by society. This paper collects evidence on the effects of the intake of anabolic androgenic steroids in the body, to generate awareness among potential users, and create policies for prevention against indiscriminate use of these substances.
It is widely appreciated that premenopausal women have a lower risk for coronary artery disease (CAD) than do men, and that this risk increases in postmenopausal women (1,2).The effects of estrogens on plasma lipids and other factors affecting coronary risk in women have been studied extensively, and are reviewed elsewhere (3–5). The contributions of gonadal steroids to coronary risk in men have received less attention. This chapter reviews the effects of androgens and estrogen on plasma lipids and relates these data to the increased coronary risk associated with male gender.
In many chronic illnesses, such as those associated with the human immunodeficiency virus (HIV), end stage renal disease, chronic obstructive lung disease, and some types of cancer, we can now achieve disease stability, but not cure. In these chronic disorders, muscle wasting occurs frequently, and is associated with debility, impaired quality of life, and poor disease outcome (1-11). For instance, a substantial proportion of HIV-infected men with acquired immunodeficiency syndrome (AIDS) require assistance with activities of daily life after hospitalization for secondary illnesses. Therefore, strategies that can reverse muscle wasting and augment muscle function may improve quality of life and reduce utilization of health care resources.
The 2000 US census data has demonstrated that the number of older men is growing faster than the number of older women. In comparison to the 1990 census, the number of men over the age of 65 yr has increased by 15%, whereas the number of women over that age has increased 10%. In absolute numbers, older women still outnumber older men, but the gap between the genders in closing. This has many potential implications in regards to aging men’ s health issues and surely will add impetus to trying to bring more clarity to the topic of male hormone replacement for older men (male HRT, or androgen replacement therapy [ART]).
Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety.
Side effects of androgen androgen therapy may be directly related to the biological actions of testosterone itself or one of its physiological metabolites (dihydrotestosterone or estrogens). Side effects may further be due to chemical modifications of the testosterone molecule. Therefore, some aspects and consequences of these modifications will be discussed briefly in this chapter. Mesterolone (a derivation of androstenedione), dihydrotestosterone (DHT) and anabolic steroids will also be touched upon.
In elderly women, after the menopause, which marks the end of reproductive life, estrogen production and plasma levels represent only a small fraction of levels during reproductive life. This decrease in estrogen production is responsible for a series of signs and symptoms characteristic of, or complicating the menopause, which as a rule react favorably to estrogen substitution.
The first experimental proof that the testes produce a substance responsible for virility was provided by Berthold (1849). He transplanted testes from roosters into the abdomen of capons and recognized that the animals with the transplanted testes behaved like normal roosters: “They crowed quite considerably, often fought among themselves and with other young roosters and showed a normal inclination to hens”. Berthold concluded that the virilizing effects were exerted by testicular secretions reaching the target organs via the bloodstream. Berthold’s investigation is generally considered the origin of experimental endocrinology (Simmer and Simmer 1961). Following his observation various attempts were made to use testicular preparations for therapeutic purposes. The best known experiments are those by Brown-Séquard (1889), who tried testis extracts on himself (which can at best have had placebo effects). The first testicular extracts with demonstrable biological activity were prepared by Loewe and Voss (1930) using the seminal vesicle as a test organ. Finally, the groundstone for modern androgen therapy was laid when steroidal androgens were first isolated from urine by Butenandt (1931), testosterone was obtained in crystalline form from bull testes by David et al. (1935) and testosterone was chemically synthesized by Butenandt and Hanisch (1935) and Ruzicka and Wettstein (1935).
Cancer of the prostate is presently the most frequently diagnosed cancer and the second most frequent cause of death due to cancer in men in many Western countries, including the US (1). The causes of prostate cancer are poorly understood, in part due to the very old age of most prostate cancer patients, which impedes epidemiological studies (1). Androgenic steroid hormones have been implicated in the etiology of prostate cancer, because many prostate carcinomas are androgen-sensitive, and a role of estrogens has also been suggested (1,2). The purpose of this paper is to attempt to apply the traditional carcinogenic risk-assessment process (3,4) to prostate cancer risk and exposure to androgenic and estrogenic hormonal agents. A major problem in this respect is that significant endogenous as well as exogenous sources of androgenic and estrogenic substances exist, while carcinogenic risk assessment is usually only applied to exogenous agents. Nevertheless, as long as essential information exists, such as dose-response data, it is possible to apply the basic elements of the carcinogenic risk-assessment process, hazard identification, analysis of dose-response data, exposure assessment, and risk characterization and evaluation (3). Risk management, i.e., prevention of prostate cancer, will only be touched upon.
Men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in male hypothalamic-pituitary-gonadal axis function: testosterone levels decline through both central (pituitary) and peripheral (testicular) mechanisms. Age-associated hypothalamic-pituitary-gonadal axis dysfunction, which has been termed 'andropause', is thought to be responsible for a variety of symptoms experienced by elderly men, such as reduced muscle and bone mass, fatigue, sexual dysfunction (including erectile dysfunction and loss of libido) and depression. Although it has been difficult to establish correlations between these symptoms and plasma testosterone levels, there is some evidence that testosterone replacement in middle-aged men leads to symptom relief, particularly with respect to muscle strength, bone mineral density and sexual dysfunction. However, there is limited evidence of a link between hypothalamic-pituitary-gonadal axis dysfunction and depressive illness, and exogenous androgens have not been shown to be antidepressant. This article focuses on the relationship between androgens and mood in aging men and highlights clinical issues relevant to the treatment of age-related depression with exogenous testosterone.
Many drugs, both therapeutic and recreational, alter the function of the pituitary gland, usually as a side effect unrelated to the primary indication for which the drug was given. Consumption of beverages containing ethanol may alter pituitary function in several ways: by direct effects on the brain or pituitary gland; by altering the function of end organs (e.g., testis) and provoking feedback-mediated changes in pituitary hormone secretion; and by modifying the peripheral metabolism or action of hormones with resulting effects on pituitary function. In some studies, the acute administration of ethanol has been reported to stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion. Cigarette smoking results in the acute release of several pituitary hormones, and the effects appear to be due to nicotine. Several studies have reported increases in plasma cortisol, DHEA, ACTH and bendorphin/ β-lipotropin in response to smoking one or more medium- or high-nicotine cigarettes; sham smoking or smoking low-nicotine cigarettes had no such effect. Acute administration of opiates (e.g., morphine, heroin, codeine, fentanyl, β-endorphin, enkephalins) has profound and generally consistent effects on human pituitary function. In males, serum LH is lowered, followed by a fall in serum testosterone. In females, opiates suppress serum LH in premenopausal subjects, often resulting in irregular menses or amenorrhea. Effects of various other substances and hormones are discussed in this chapter.
GnRH antagonists have been developed in large part because of their potential use as contraceptive agents, particularly in men. Specifically, it was hoped that GnRH antagonists combined with testosterone (T) would be a more effective contraceptive regimen than T alone. We compared the suppressive effects of a potent GnRH antagonist, Na1-Glu [AcD2NaL1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),+ ++DAla10-GnRH], and of T together and separately on serum and urinary gonadotropin and serum inhibin levels in normal men. Ten-day courses of Nal-Glu (75 micrograms/kg; Nal-Glu alone), 200 mg testosterone enanthate, im, on days 0 and 7 (T alone), and the combination (Na1-Glu + T) were given to nine men. Serum gonadotropin and inhibin concentrations decreased after 1-2 days of Na1-Glu administration, while gonadotropin suppression occurred more slowly after T alone. Serum T fell to 30% of baseline values during Na1-Glu administration. The combination of Na1-Glu + T was more effective in suppressing serum LH, FSH, and inhibin than was either Na1-Glu alone or T alone. All hormone levels returned to baseline levels within 2.5 weeks after the end of the three regimens. We conclude that the Na1-Glu GnRH antagonist effectively inhibits gonadotropin, inhibin, and sex steroid secretion when given daily for 10 days and that the administration of Nal-Glu + T results in more complete gonadotropin and gonadal suppression than that produced by either agent given alone. These results encourage further investigation of the combination of a GnRH antagonist and T as a male contraceptive regimen and of the antagonist alone as a treatment for hormone-dependent neoplasia.
The use of anabolic-androgenic steroids (AS) is perceived by the media, by segments of the sports medicine and athletic communities, and by the public to have grown to epidemic proportions. Unfortunately, the incidence and prevalence of AS use among elite, amateur, and recreational athletes is poorly documented. This study was designed to help identify AS use patterns among the male portion of the general adolescent population. The overall participation rate on a schoolwide basis was 68.7% and on an individual basis reached 50.3%. Participants in this investigation were 12th-grade male students (N = 3403) in 46 private and public high schools across the nation who completed a questionnaire that established current or previous use of AS as well as user and nonuser characteristics. Results indicate that 6.6% of 12th grade male students use or have used AS and that over two thirds of the user group initiated use when they were 16 years of age or younger. Approximately 21% of users reported that a health professional was their primary source. The evidence indicates that educational intervention strategies should begin as early as junior high school; the intervention should not be directed only toward those individuals who participate in school-based athletics.
The specific roles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in controlling human spermatogenesis are poorly understood. We studied the effect of an experimentally induced, selective LH deficiency on sperm production in normal men. After a 3-mo control period, five men received 200 mg testosterone enanthate (T) i.m./wk to suppress LH, FSH, and sperm counts. Then, while continuing T at the same dosage, human FSH (hFSH) was administered simultaneously to replace FSH activity, leaving LH activity suppressed. Four men received 100 IU hFSH s.c. daily plus T (high dosage hFSH) for 13-14 wk, while one man received 50 IU hFSH s.c. daily plus T (low dosage hFSH) for 5 mo. The effect on sperm production of the selective LH deficiency produced by hFSH plus T administration was assessed. In the four men who received the high dosage hFSH regimen, sperm counts were markedly suppressed during T administration alone (0.3+/-0.2 million/cm(3), mean+/-SE, compared with 94+/-12 million/cm(3) during the control period). Serum LH bioactivity (determined by in vitro mouse Leydig cell assay) was suppressd (140+/-7 ng/ml compared with 375+/-65 ng/ml during control period) and FSH levels (by radioimmunoassay) were reduced to undetectable levels (<25 ng/ml, compared with 98+/-21 ng/ml during control period) during T alone. With the addition of 100 IU hFSH s.c. daily to T, sperm counts increased significantly in all subjects (33+/-7 million/cm(3), P < 0.02 compared with T alone). However, no subject consistently achieved sperm counts within his control range. Sperm morphology and motility were normal in all four men and in vitro sperm penetration of hamster ova was normal in the two men tested during the hFSH-plus-T period. During high-dosage hFSH administration, serum FSH levels increased to 273+/-44 ng/ml (just above the normal range for FSH, 30-230 ng/ml). Serum LH bioactivity was not significantly changed compared with the T-alone period (147+/-9 ng/ml). After the hFSH-plus-T period, all four men continued to receive T alone after hFSH was stopped. Sperm counts were again severely suppressed (0.2+/-0.1 million/cm(3)), demonstrating the dependence of sperm production on hFSH administration. Serum T and estradiol (E(2)) levels increased two- to threefold during T administration alone compared with the control period. Both T and E(2) levels remained unchanged with the addition of hFSH to T, confirming the lack of significant LH activity in the hFSH preparation. In the one man who received low dosage hFSH treatment, sperm counts were reduced to severely oligospermic levels, serum FSH was suppressed to undetectable levels, and serum LH bioactivity was markedly lowered during the T-alone period. With the addition of 50 IU hFSH s.c. daily to T, sperm counts increased, to a mean of 11+/-3 million/cm(3). During this period, serum FSH levels increased to a mean of 105+/-11 ng/ml (slightly above this man's control range and within the normal adult range), while LH bioactivity remain suppressed. After hFSH was stopped and T alone was continued, sperm counts were again severely reduced to azoospermic levels. We conclude that FSH alone is sufficient to reinitiate sperm production in man during gonadotropin suppression induced by exogenous T administration. FSH may stimulate sperm production in this setting by increasing intratesticular T through androgenbinding protein production or by increasing the sensitivity of the spermatogenic response to the intratesticular T present during exogenous T administration.
The role of follicle-stimulating hormone (FSH) in the control of spermatogenesis is not well established in any species, including man. We studied the effect of an experimentally-induced, selective FSH deficiency on sperm production in normal men. After a 3-mo control period, five normal men received testosterone enanthate (T) 200 mg i. m. weekly to suppress luteinizing hormone (LH) and FSH, until three successive sperm counts revealed azoospermia or severe oligospermia (sperm counts <3 million/ml). Then, while continuing T, human chorionic gonadotropin (hCG) 5,000 IU i. m. three times weekly was administered simultaneously to replace LH activity, leaving FSH activity suppressed. The effect of the selective FSH deficiency produced by hCG plus T administration on sperm production was determined. Sperm counts (performed twice monthly throughout the study) were markedly suppressed during T administration alone (1.0+/-1.0 million/ml mean+/-SE, compared with 106+/-28 million/ml during the control period, P < 0.001). With the addition of hCG to T, sperm counts returned toward normal (46+/-16 million/ml, P < 0.001 compared with T alone). In two subjects, sperm counts during hCG plus T returned into the individual's control range. Sperm motility and morphology were consistently normal in all men during hCG plus T. Serum FSH levels by RIA were normal (110+/-10 ng/ml) in the control period and were suppressed to undetectable levels (<25 ng/ml) in the T alone and hCG plus T periods. Urinary FSH excretion was markedly suppressed in the T alone (60+/-15 mIU/h-2nd IRP, P < 0.01) and hCG plus T (37+/-9 mIU/h, P < 0.01) periods compared with the control period (334+/-78 mIU/h). We conclude that spermatogenesis as assessed by sperm counts, motilities, and morphologies may be reinitiated and maintained at normal levels in men with undetectable blood FSH levels and urinary excretion of FSH less than that of prepubertal children. This conclusion implies that, although FSH may exert effects on human testicular function, maintenance of normal spermatogenesis and reinitiation of sperm production after short-term suppression by exogenous steroids can occur in spite of nearly absent FSH stimulation.
Testosterone enanthate (TE) was administered im to 39 normal adult men (age 21–39) to assess its efficacy as a suppressor of spermatogeneis and to determine possible adverse effects. 17 subject (Group A) received TE (200 mg/week) for 16 to 20 weeks. 16/17 lowered sperm counts (SC) to < 5 million/cc; 11/17 to < 300 000; and 10/17 became azoospermic. Group B received TE (200 mg/weeks); in 10/22 SC were < 5 million/cc at 16 weeks; 9/22 to < 300 000; and 5/22 azoospermic; when those with SC > 5 million/cc were switched to weekly treatment (additional 3–16 weeks), 9/12 lowered SC to < 5 million/cc. Overall, 19/22 of Group B attained this level. Serum LH and FSH were decreased on both regimens. These effects were dose-related. Mean serum testosterone was elevated above control (64%) in Group A, but remained at basal levels 2 weeks after TE injection in Group B. Decreasing the frequency of TE (3 or 4 weeks) resulted in a rebound of FSH and LH above baseline and increased SC. After discontinuing treatment, sperm counts and hormonal measurements returned to normal. Modest increase in body weight, red cell mass, oiliness of skin and mild acne were seen in some subjects. Liver function tests, glucose tolerance, blood lipids and renal function were unchanged.
The negative feedback control of serum gonadotropins by sex steroids was studied in eight men with Leydig cell insufficiency, four of whom with unmeasurable Leydig cell function. Mean serum LH and FSH concentrations, the pattern of LH pulsatile release, and the response of gonadotropins to LRH stimulation were studied before and at the completion of 4-day continuous infusions of testosterone (T; 15 mg/day), 17β-estradiol (E; 90 μg/day), and 5α-dihydrotestosterone (DHT; 7.0 mg/day). Both T and E infusion resulted in approximately 30% suppression of mean serum LH and FSH concentrations in hypogonadal subjects; these responses were similar to those of normal men. Neither T nor E infusion produced a decrease in LH pulse frequency or amplitude in hypogonadal men. This differs from the decrease in LH pulse frequency seen with T and the fall in LH pulse amplitude during E infusion observed in normal men. The fall in mean serum LH concentration during infusion of the nonaromatizable andorgen DHT was significantly less in the hypogonadal (11 ± 2.7%) than in the normal men (35 ± 10%; P<0.05). DHT resulted in an augmentation of the LH response to LRH administration in normal men, which was not observed in the hypogonadal men. No significant FSH suppression by DHT was seen in either group. The data indicate that the modulation of LH by sex steroids in men with primary hypogonadism appears to differ from normal in that there is a resistance to the effects of pure androgen. The mechanism for this resistance remains to be determined.
To determine if high intratesticular concentrations of testosterone are essential for completion of spermatogenesis, intact 90-day-old Charles River CD rats were treated with testosterone propionate (TP). Pilot studies indicated that sc administration of 100 μg TP/100 g BW.day caused maximum suppression of testicular testosterone. This dose was administered for 13 days and animals were killed 24 h after the last injection. Intratesticular levels of testosterone were reduced 30-fold from 0.295 ± 0.04 to 0.01 ± 0.001 ng/mg testis, and serum levels of FSH were suppressed 33% from 238 ± 15 to 195 ± 5 ng/ml (P<0.001). However, testicular weight only fell from 1.598 ± 0.058 to 1.482 ± 0.026 g, and qualitatively, spermatogenesis was normal. To examine the possibility that morphological changes failed to occur because the period of treatment was too short, a second group of animals were treated with the same dose of TP for 39 days. Once again, the intractesticular concentration of testosterone was suppressed from 0.196 ± 0.35 to 0.006 ± 0.002 ng/ml testis (P < 0.001) and the serum concentration of FSH was reduced from 298 ± 53 to 205 ± 34 ng/ml (P < 0.05). Testicular weight only fell from 1.660 ± 0.028 to 1.455 ± 0.057 g, and complete spermatogenesis occurred. At this interval, however, a few abnormal and probably dysfunctional Sertoli cells as well as some degenerating pachytene spermatocytes and spermatids were observed. In the testis, the amount of androgen-binding protein fell from 16.34 ± 1.14 to 6.65 ± 0.99 pM/testis (P < 0.001), but it was not significantly altered in the epididymis. These observations indicate that persistance of complete spermatogenesis in the adult rat is not dependent upon high intratesticular levels of testosterone and suggest that FSH, which is known to regulate Sertoli cell function, may, as a result, secondarily influence germ cell maturation.
Testosterone (T) administration slows LH pulse frequency in man, presumably by an effect on the hypothalamic GnRH pulse generator, but it also may have a direct action on the pituitary. To determine if T does indeed affect gonadotropin secretion by acting directly on the pituitary, we studied the effect of T on GnRH-stimulated gonadotropin secretion. Six men with hypogonadotropic hypogonadism were treated with physiological doses of GnRH (5 micrograms every 2 h, sc by automatic infusion pump) for 6 weeks. Once their gonadotropin levels were normal, the men received a supraphysiological dosage of T enanthate (200 mg, im, weekly for 8 weeks) in addition to GnRH. They then received GnRH alone for a final 8-week period. Blood sampling was performed every 10 min for 8 h at the end of each of the three study periods. T administration suppressed the mean serum LH level to about 50% of the value during GnRH alone [18 +/- 2 (+/- SE) vs. 37 +/- 2 micrograms/L; P less than 0.05] and suppressed the mean serum FSH level to about 30% of the value during GnRH alone (39 +/- 6 vs. 128 +/- 28 micrograms/L; P less than 0.05). Eight weeks after stopping T, while continuing GnRH alone, serum LH and FSH levels were similar to those at the end of the first period of GnRH administration. The mean LH response to GnRH was reduced during T administration (17 +/- 3 micrograms/L) compared to that during the initial period of GnRH alone (31 +/- 4 micrograms/L; P less than 0.05). Serum T and estradiol levels were in the low normal range after GnRH alone before T administration (11 +/- 2 nmol/L and 105 +/- 17 pmol/L, respectively) and increased to just above the normal adult ranges after 8 weeks of T administration (36 +/- 5 nmol/L and 264 +/- 49 pmol/L, respectively). These results demonstrate that T and/or its metabolites inhibit LH and FSH secretion by a GnRH-independent mechanism, probably directly on the pituitary gland, in man.
The problem of extrapolating effects of reproductive toxins on experimental animals to predict the doses that would produce infertility in human males is discussed using published data on effects of testosterone and estradiol on sperm production in the rat, rabbit, rhesus monkey, ram, stallion, and humans. This analysis indicates that calculation of the dose of testosterone that reduces human sperm counts by a given percentage is best done using the dose administered to laboratory animals expressed on the basis of body weight, as opposed to some other parameter such as body surface area. A survey of the available data in the literature indicates the incompleteness of the data set and the specific information needed to improve the basis for extrapolation. Nevertheless, we can predict from studies on laboratory animals the dose of testosterone necessary to reduce sperm counts in humans within a factor of 2.
In male contraceptive trials, approximately half of normal men become azoospermic on high dosages of testosterone enanthate (TE), whereas the other half of men become severely oligozoospermic. To determine whether sperm function is reduced in men with severe oligozoospermia induced by TE, we studied sperm function in six normal men whose sperm counts were reduced to less than or equal to 5 X 10(6)/ml but not to azoospermia by high-dosage TE administration for 5 to 6 months and five normal men who received placebo (sesame oil) injections for the same period of time. Seminal fluid analysis and sperm function (as assessed by zona pellucida-free hamster ova penetration test, HOPT) were performed during a pretreatment period and after at least 3 months of TE or placebo treatment. HOPT was severely reduced in all six men, whose sperm counts were suppressed to severe oligozoospermia during TE (0.8 +/- 0.8% compared to 37 +/- 14% during the pretreatment period, P less than 0.05). Five men failed to penetrate any hamster ova, while the remaining man penetrated only 5% of ova during TE treatment. There were no significant changes in other seminal fluid measurements during high-dosage TE. The five men who received placebo injections did not demonstrate any significant changes in HOPT or seminal fluid analysis during the treatment period. In summary, we found that the fertilizing capacity of sperm is markedly diminished when sperm production is severely reduced by high-dosage TE administration. These findings suggest that male contraception may be achievable by reduction of spermatogenesis to severe oligozoospermia.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to investigate whether testosterone can maintain spermatogenesis in the absence of FSH in primates, four cynomolgus monkeys were hypophysectomized and implanted with 20 5-cm-long testosterone-filled silastic capsules within 45 min of pituitary ablation. Thereafter the serum levels of testosterone were elevated about 9-fold over presurgical levels. Testicular volumes declined to 60% of presurgical values. Testicular concentrations of testosterone were 50-180% of presurgical levels. Germ cell numbers were reduced to 30-50% of presurgical values and germ cell ratios suggested that the reduced numbers of all advanced germ cells were due to a decrease in the efficiency of proliferation of B spermatogonia. A fifth monkey was left untreated following hypophysectomy. Its serum testosterone was as low as that of castrated monkeys, and the testicular volume declined to 30% of that before surgery. Primitive spermatogonia were the only germ cells present 13 weeks after surgery. Thus, in primates testosterone alone maintains the complete process of spermatogenesis, however, spermatogonial proliferation is impaired in the absence of FSH.
This study was designed to investigate the effect of pharmacologic doses of testosterone on serum FSH and LH levels in normal males. Testosterone proprionate, 100mgm, was administered intramuscularly daily for four days to four normal males. Serum samples for FSH and LH were collected from each subject daily before, during and for four days following the injections of testosterone. As anticipated, serum LH levels promptly suppressed to undetectable levels. Serum FSH levels suppressed significantly to 60–70% of baseline values in all four subjects. These results suggest that testosterone may have some part in the control of serum FSH as well as LH levels in normal males.
Serum LH and FSH levels were measured by radioimmunoassay after exogenous testosterone was administered to four groups of adult males in dosages ranging from 1–25 mg per day. Serum testosterone concentrations, determined by radioimmunoassay, were elevated subsequent to the administration of the higher dosages. Dose-related depression of both LH and FSH was observed subsequent to administration of 5 or more mg of testosterone per day; the smallest dosage (1 mg) was not associated with any consistent changes in LH or FSH. The rate and extent of decline of the two gonadotropins differed. Serum LH values tended to drop and recover more rapidly than FSH following testosterone administration. These results indicate that testosterone suppresses serum levels of both LH and FSH in the human adult male. There was no evidence of stimulation of gonadotropin release at these doses.
Studies on the role of sex steroids in the feedback control of follicle stimulating hormone (FSH) concentrations in 22-35 year old men are reported. 10 normal volunteers and 8 men undergoing evaluation for azoospermia or oligospermia received steroids by constant infusion for 96 hours at twice the estimated daily production rate of normal men to obtain stable levels in peripheral blood. 15 mg of testosterone increased plasma testosterone and estradiol levels 2-fold and suppressed FSH and luteinizing hormone (LH) approximately 40% during infusion Days 3 and 4. 90 mcg of estradiol/day caused similar suppression of FSH and LH and the addition of 4.5 mg of 17 alpha-hydroxyprogesterone had no additive effect. 7.5 mg of dihydrotestosterone/day produced no detectible changes in FSH or LH. No evidence for a selective effect of any of the steroids on FSH secretion was seen. These data support the concept that although there is a specific seminiferous tubular factor regulating FSH secretion, testicular steroids also modulate FSH secretion.
The mechanism by which treatment with testosterone produces azoospermia was investigated in adult male rats. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured in rats treated with testosterone in order to determine whether testosterone in doses which suppressed only LH, and not FSH, would produce atrophy of the germinal epithelium. Rats received injections of testosterone enanthate (TE), (.3, 3, or 30 mg), 3 times weekly for 6 weeks. Low dose TE (.3 mg): 1) decreased mean testis weight by 42%, 2) produced atrophy of the germinal epithelium, and 3) suppressed serum LH but not FSH. High dose TE (3 and 30 mg): 1) did not affect testis weight, 2) did not affect the histology of the germinal epithelium, and 3) did suppress both LH and FSH. It is concluded that testosterone induces germinal atrophy by suppressing serum LH concentrations and subsequent androgen production by the Leydig cells, thereby decreasing the normally high intratesticular levels of androgen which are necessary for maintenance of the germinal epithelium. When these high concentrations of androgen are restored by treatment with pharmacologic doses of testosterone, no disturbance of the germinal epithelium occurs despite suppression of both LH and FSH.
Testicular and plasma testosterone (T) and plasma LH levels were determined in 6 normal men. Two of these men received 50 mg testosterone propionate (TP) daily for 10 and 25 weeks, respectively. Testicular and plasma T and plasma LH assays were again performed during TP administration. The mean T concentration for 5 control testicular biopsies was 553 ng/g ± 90 sd, which was approximately 100 times higher than average normal plasma T concentrations (assuming 1 ml plasma 1 g tissue). Administration of TP resulted in the following: 1) LH was rapidly reduced to undetectable levels; 2) testicular T decreased by about 95%; 3) plasma T increased nearly 2 fold; and 4) sperm concentration dropped sharply. Since a high concentration of testicular T is known to be required for normal spermatogenesis, we conclude that the cause of the depression of spermatogenesis in men given TP is the striking reduction in testicular T.
The effect of 'low' and 'high' constant infusion doses for 48 hr of testosterone (T), estradiol (E2), dihydrotestosterone (DHT), and 17α hydroxyprogesterone (17 OHP) were studied in 13 normal men. Four control infusions of normal saline were performed for comparison. The slope of the line for the control studies was not statistically different from zero. Plasma T, LH, and FSH were measured, using established competitive binding or radioimmunoassay methods. Measurements were made every 6 hr during and every 12 hr following the infusion. 'Low' doses of T (7 mg/day/1.7 m2) significantly (P<0.05) suppressed LH by 50% within 48 hr in all subjects without increasing plasma T above physiological levels in blood. No significant suppression of FSH was observed at this dose. At the conclusion of the infusion, T fell below 200 ng/100 ml, and returned to baseline within 24 hr. 'High' doses of T (35 mg/day/1.7 m2) significantly suppressed both LH and FSH. DHT, an androgen incapable of conversion to a known estrogen (7 mg/1.7 m2/24 hr) significantly suppressed LH by 48 hr but not FSH in all subjects studied. DHT suppression trend was less than that of testosterone. The overall effect of T could be the result either of T as an androgen, or the result of peripheral conversion to an estrogen. E2 (40 μg/day/1.7 m2) significantly reduced LH in all five studies and suppressed T within 12 hr. The effect upon LH was less than that of the testosterone infusion. The E2 infusion had no significant effect on assayable FSH levels within 48 hr unless a 'high' amount (200 μg/day/1.7 m2) was given. 17α Hydroxyprogesterone, a major testicular secretion product (2 mg/day/1.7 m2) did not lower LH or FSH. These results indicate that a dose of testosterone which mimics normal blood production rate acting either as an androgen or as an estrogen is a major factor in the control of LH.
In experimental animals, primary testicular deficiency leads to increased LH pulse frequency. Pulsatile FSH secretion has not been well characterized in any species. To determine the effect of testosterone (T) on the pattern of pulsatile gonadotropin secretion in man, we performed frequent blood-sampling studies in six normal men and six men with primary hypogonadism. All primary hypogonadal men were studied 6-8 weeks after stopping T replacement therapy. Five of the six hypogonadal men were restudied 6-8 weeks after treatment with T enanthate (200 mg, im, every 2 weeks; sampling in this group was 2 weeks after their last T injection). Blood sampling was done at 10-min intervals for 12 h in all subjects, and the pattern of episodic LH and FSH secretion was determined. Normal men had a serum T level of 6.3 +/- 0.3 ng/ml (mean +/- SEM), a LH level of 34 +/- 3 ng/ml, and a LH pulse pattern characterized by low frequency (7.6 +/- 0.7 pulses/12 h) and low amplitude (16 +/- 1 ng/ml). Compared to normal men, primary hypogonadal men had a significantly lower T level (2.9 +/- 0.4 ng/ml) and significantly higher LH pulse frequency (13.0 +/- 1.3 pulses/12 h), amplitude (51 +/- 7 ng/ml), and mean level (222 +/- 26 ng/ml). Reinstitution of T replacement therapy in hypogonadal men resulted in a significant increase in the T level (4.7 +/- 0.5 ng/ml) and significant decreases in LH pulse frequency (7.2 +/- 1.6 pulses/12 h) and amplitude (41 +/- 5 ng/ml) as well as mean LH level (75 +/- 15 ng/ml). FSH levels fluctuated in a distinctly pulsatile pattern in all three groups. Differences in pulsatile FSH secretion between primary hypogonadal men before and during T therapy and normal men paralleled those in pulsatile LH secretion in both frequency and amplitude. These results demonstrate that in man 1) diminished T negative feedback results in high frequency (circhoral), high amplitude LH and FSH pulses; 2) T replacement decreased LH and FSH pulse frequency and amplitude as well as mean levels; and 3) the decreased LH and FSH pulse frequency with T treatment implies that T or a metabolite of T acts on the central nervous system to slow the hypothalamic LHRH pulse generator.
Serum reproductive hormone levels were measured serially after eugonadal and hypogonadal men had received either a 200-mg or a 100-mg intramuscular injection of testosterone enanthate. The calculated mean integrated testosterone and estradiol levels indicated that the 200-mg testosterone enanthate injection in the hypogonadal subjects maintained eugonadal levels of these hormones through day 11. The 100-mg dose maintained eugonadal levels of these hormones through day 11. The 100-mg dose maintained eugonadal testosterone levels through day 7. The testosterone:estradiol ratios in both groups following the 200-mg injection remained above or at the eugonadal baseline trough day 21. The authors recommend that replacement therapy for hypogonadal men should be 200 mg of testosterone enanthate every 10 to 14 days. A similar dosage would be recommended if testosterone enanthate were to be used as an experimental inhibitor of spermatogenesis (contraceptive agent).
Excessive gonadotropin stimulation of the testis induced by the administration of high doses of hCG or LH markedly decreases testicular function in experimental animals. The adverse effects of supraphysiological gonadotropin stimulation are thought to be mediated, in part, by the very high levels of estradiol produced. We administered a supraphysiological dosage of hCG together with exogenous testosterone (T) to normal men for several months. The combination of these agents produced very high serum estradiol (E 2) levels and (we assume) high intratesticular E 2 levels. In this setting of supraphysiological gonadotropin stimulation and high E 2 levels, we examined serum levels of T, the Δ 4 and Δ 5 steroid precursors of T, and sperm production. After a 3-month control period, five normal men received T enthanate (T; 200 mg, im, weekly) for 3-5 months. Then, while T was continued in the same dosage, all subjects were given hCG (5000 IU, im, three times weekly) for an additional 4-6 months. Serum E 2 levels during hCG plus T treatment increased to a mean (±SEM) of 158 ± 16 pg/ml. Despite the very high E 2 levels generated by this prolonged administration of hCG and T, hCG stimulated a mean increase of 5.1 ng/ml in the total T level and 0.18 ng/ml in the free T level over those found during T administration alone. These increments in T levels approximate normal blood T levels in man. Significant changes in serum levels of Δ 4 steroid precursors of T biosynthesis occurred during the study. Serum progesterone and 17-hydroxyprogesterone levels fell significantly with gonadotropic suppression induced by T administration alone and then increased significantly with hCG stimulation. In contrast to the changes seen in serum levels of Δ 4 precursors, there were no significant changes in levels of Δ 5 steroid precursors of T biosynthesis. An increased ratio of 17-hydroxyprogesterone to T during hCG administration was the only suggestion of an E 2-induced block in steroid synthesis. hCG also significantly stimulated sperm production, as assessed by sperm concentration, motilities, and morphologies, in spite of the very high serum E 2 levels; the mean sperm concentration increased from 1.0 ± 1.0 million/cc during T administration alone to 46 ± 16 million/cc during hCG plus T treatment. We conclude that chronic administration of supraphysiological dosages of hCG can stimulate testicular function in man, despite very high E 2 levels, and that hCG in these dosages does not lead to severe testicular regression in man. Perhaps a higher dosage of hCG administered to men would replicate the severe testicular suppression reported in experimental animals.
Proceedings, hormonal control of male fertility. Publication no. NIH 78-1097
- Patanelli
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Patanelli DJ, ed. Proceedings, hormonal control of male fertility. Publication no. NIH 78-1097. Washington DC: US DHEW; 1977.