Sperm Suppression Research Articles

Testosterone and male contraception.

Rates of unintended pregnancy have remained relatively stagnant for many years, despite a broad array of female contraceptive options. Recent restrictions on access to abortion in some countries have increased the urgency for expanding contraceptive options. Increasing data suggest men are keen to utilize novel reversible male contraceptives. Despite decades of clinical research in male contraception, no reversible hormonal product currently exists. Nestorone/testosterone, among other novel androgens, shows promise to finally move to pivotal Phase 3 studies and introduction to the marketplace. Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit negative feedback that regulates the hypothalamic-pituitary-testicular axis. By suppressing release of gonadotropins, these agents markedly decrease endogenous testosterone production, lower intratesticular testosterone and suppress spermatogenesis. The addition of a progestin enhances the degree and speed of sperm suppression. The androgen component preserves a state of symptomatic eugonadism in the male. There is growing demand and acceptance of male contraceptive options in various forms. As these formulations progress through stages of drug development, regulatory oversight and communication with developers around safety and efficacy standards and garnering industry support for advancing the production of male contraceptives will be imperative.

Regulatory challenges of new male contraceptive methods.

Progress in male contraception development faces the challenge of a lack of regulatory precedent and guidelines on the evidence (trial design and primary endpoint) required for marketing approval. Moreover, the development of a male contraceptive is complicated by the fact that the clinical treatment effect; prevention of pregnancy, is not measured in the patient receiving the intervention. Regulatory precedent and guidelines exist for female hormonal contraceptives but their applicability to male contraceptive products likely varies based on the mode of action and the anticipated pharmacodynamic effects of the product. The unique attributes of male contraceptives, including the frequent delay between the intervention (e.g., vasectomy and hormonal methods) and ultimate contraceptive effect, sperm suppression near azoospermia, and pregnancy prevention need to be addressed. This article describes the regulatory challenges faced by developers of male contraceptive products and offers proposals, paving the way for the development of both hormonal methods and non-hormonal approaches. Our article intends to suggest the directions but cannot substitute for the advice of regulatory agencies.

Advancements in Male contraceptives: A flanged approach in family planning

According to 2019 reports, WHO estimated that around 214 million women of reproductive age in developing regions have an unmet need for contraception either due to limited needs or availability. With the aid of Aritifical Intelligence we can find other alternatives and also possbile approaches for Contraception The aim of this review article is to emphasize the need for combination of testosterone and nestorone in male contraceptives. The use of contraception is a widely acknowledged method of population control. Women have always been the main target of hormonal contraceptive treatments. The use of hormonal and non-hormonal techniques for male contraception is a desirable choice. Testosterone-based hormonal contraception has had positive outcomes. Reversible techniques of male contraception without hormones, such as reversible sperm suppression with guidance, are extremely promising. This manuscript tries to encompass various methods of contraception like hormonal and non-hormonal which would serve in efficient contraception.

Male contraception development: monitoring effective spermatogenesis suppression utilizing a user-controlled sperm concentration test compared with standard semen analysis

To determine whether a user-controlled sperm concentration test compared with standard semen analysis can effectively monitor spermatogenesis suppression for male contraception. Single center, prospective sub study of the ongoing clinical trial: "Study of daily application of Nestorone and testosterone combination gel for male contraception." Research institute at an academic medical center. Couples participating in the male contraceptive clinical trial. None. The ability by participants to monitor sperm suppression to a threshold compatible with contraceptive efficacy utilizing a user-controlled test verified by sperm concentration determined by standard laboratory methods. Thirty-eight men participating in a hormonal male contraceptive clinical trial provided multiple samples during spermatogenesis suppression for this substudy. Participants, employing a user-controlled test, correctly identified the absence of sperm (a negative test) in 100% of their laboratory-confirmed azoospermic samples (n = 122). Participants also identified 100% of samples (n = 73) with sperm >0.2 million/mL as positive. Sperm counts between 0.01 and 0.2 million/mL were identified as negative in 96% of samples. Trial participants noted the overall ease of using the test with respect to sample preparation, test timing, and result interpretation, and that they could accurately use this test at home without difficulty. Participants undergoing spermatogenesis suppression in a hormonal male contraceptive trial performed user-controlled test to determine whether their semen sperm concentration was ≤ or >0.2 million/mL. Compared with standard semen analyses, participants correctly identified 100% of samples with sperm counts >0.2 million/mL as positive (Sensitivity 100%). A positive result when the couple is using a male contraceptive method triggers the need for semen analysis by a laboratory while the couple uses another method of contraception. Participants correctly diagnosed samples ≤0.2 million sperm/mL as negative in 99% of samples (specificity 99%). A negative result indicates a sperm concentration ≤0.2 million/mL, well below the threshold of ≤1 million/mL offering contraceptive efficacy demonstrated by prior studies. At-home sperm concentration test would minimize the need for users to return to the clinic to monitor suppression of spermatogenesis, decreasing cost and burden of male contraception trials and increasing practicality of the method. NCT:03452111.

Contraception across transgender.

Sexual and reproductive issues are essential elements of well-being in cisgenders as well as for the transgender population. Gender-affirming hormonal treatments (GAHTs) aim to induce phenotypical changes congruent with the desired gender and subsequent reduction of gender dysphoria. While genital surgical procedures including hysterectomy and/or adenectomy cause permanent loss of ability to conceive, GAHT may induce a varying degree of reversible loss of fertility. For these reasons, transgender men and women need to be counseled concerning contraceptive options and potential effects of treatment on reproductive function before initiating GAHT. The literature reports that sexual activity with genital involvement is performed by less than half of transgender persons who have been sexually active with a partner in the past. Testosterone (T) is the most commonly used compound in transmen and usually leads to amenorrhea within 1-12 months from first administration, however cessation of menses does not mean anovulation. Some studies report cases of unintended pregnancies among transgender men under masculinizing therapy, therefore T treatment cannot be considered a contraceptive option. Currently available contraceptive options have pros and cons in transmen and scarce literature exists on their use. The effects of GAHT on fertility in transwomen are even less well known. Prolonged estrogen exposure induces sperm suppression and morphological changes of the spermatozoa, however the degree of resulting pregnancy protection is unclear. Further research to inform the contraceptive counseling in this population is mandatory.

A NEW METHOD FOR ACCURATE PREDICTION OF SPERMATOGENESIS: FSH/T AND T IN SEMINAL PLASMA

A NEW METHOD FOR ACCURATE PREDICTION OF SPERMATOGENESIS: FSH/T AND T IN SEMINAL PLASMA

Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10mg/20mg, NES 2mg/3mg/dose e.g. 200/300μg/day absorbed, NETA 5mg/10mg, LNG 120μg/240μg. From an andrology outpatient clinic, 56 healthy men aged 18-50years, with body mass index ≤33kg × m-2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception.

Les contraceptions du futur chez l’homme

Although many female contraceptives are available, data on uncontrolled population growth and abortion rate demonstrate that contraceptive choices are still inadequate and accessibility is poor. Broader contraceptive option is an ethical issue that would benefit not only the lives of families and women in particular but would also ensure the survival of our planet. In spite of the shortage of male contraceptives, about 30% of couples rely on a male method and men worldwide show interest in actively contributing to birth control. A variety of approaches has been undertaken in developing a male contraceptive but progress has been poor. The hormonal approach induces profound sperm production through a reversible suppression of gonadotropins and intra-testicular testosterone. In this context, androgen dependent physiological functions must be maintained by exogenous androgen administration. Hormone induced sperm suppression provides optimal pregnancy protection. Androgen-progestin regimens induce profound sperm suppression, and allow spermatogenesis to fully recover to levels consistent with normal male fertility in all men. This approach has many limitations such as the required time until sperm suppression is achieved and until fertility is regained after discontinuing. Even the most effective regimen suppresses spermatogenesis to the threshold useful for contraceptive protection in only about 90% of subjects. A recent multicenter efficacy study supported by CONRAD and the WHO tested the efficacy of the combined administration of eight weekly injections of NETE 200 mg and TU 1000 mg. The trial has been prematurely terminated due to mood-related side effects despite results show good sperm suppression and contraceptive protection.

Complete sperm suppression induced by dienogest plus testosterone undecanoate is associated with down-regulation in the expression of upstream steroidogenic enzyme genes in rat testis

BackgroundWe had shown that dienogest (DNG) + testosterone undecanoate (TU) induced complete sperm suppression in rats when administered together every 45 days. On the other hand, individual drugs given alone in a similar fashion failed to achieve the same result. Study DesignThe present study was therefore undertaken to determine the reason for such a differential sperm suppression and to correlate it with the expression of steroidogenic enzyme genes in the rat testis. ResultsAdministration of DNG (40 mg/kg body weight [bw]) + TU (25 mg/kg bw) every 45 days for a duration of 90 days induced spermatogenic arrest, leading to a significant reduction in testicular weight and number of precursor germ cells. Flow cytometric analysis further confirmed the same result, leading to a significant shift in the distribution of haploid cells. Measurement of testosterone (serum and intratesticular) was significantly low. Complete sperm suppression coincided with significant down-regulation in the expression of upstream steroidogenic enzyme genes represented serially by cytochrome P450 side-chain cleavage, P450 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein (StAR) in the testis. On the other hand, rats administered with either DNG or TU alone demonstrated incomplete sperm suppression in which the expression of all the above genes remained characteristically nonuniform. ConclusionTaken together, the above findings corroborate the fact that regulation of expression of three of the upstream steroidogenic enzymes genes and the StAR protein in rat testis is crucial in leading to complete sperm suppression as observed with DNG+TU treatment.

Extended intervention time and evaluation of sperm suppression by dienogest plus testosterone undecanoate in male rat

Background The potential of using dienogest [DNG, 40 mg/kg body weight (bw)] plus testosterone undecanoate (TU, 25 mg/kg bw) in rats for development of a once-a-month male hormonal contraceptive has been reported earlier in our laboratories. Study Design In the present study, we report a separate efficacy evaluation of the same combination, DNG (40 mg/kg bw) and TU (25 mg/kg bw) in which interval of drug administration has been extended further to 45 and 60 days instead of every 30 days. Results Complete sperm suppression was observed in rats sacrificed either 60 or 90 days after DNG+TU administration, for two injections at 45-day interval. The neutral α-glucosidase activity in these treated rats remained in the normal range. Germ cell loss due to apoptosis was frequently observed both after 60 or 90 days of combination treatment. Significant decline in serum gonadotropin and testosterone, both serum and intratesticular levels, were observed in the treated rats. Following stoppage of treatment (given at 45-day interval) after two (0 and 45 days) or three injections (0, 45 and 90 days), complete restoration of spermatogenesis was observed by 120 and 165 days, respectively. The sperm suppression, however, could not be sustained when the period of combined drug administration was extended from every 45 to 60 days. Conclusions Dienogest plus testosterone undecanoate in the above doses retained contraceptive effectiveness when administered every 45 days but not 60 days. The spermatogenic arrest was completely reversible once drug treatment is stopped. The dose and the frequency of intervention can be extrapolated in future clinical trials.

Does ethnicity matter in male hormonal contraceptive efficacy?

The development of male hormonal contraception has progressed significantly during the last three decades. The ultimate goal is to produce an effective, safe and reversible male method of contraception that are within reach of and can be used by all men globally. This review aims to outline the recent developments in male hormonal contraception with special emphasis on how ethnicity influences acceptability, extent of sperm suppression, and rate of recovery of spermatogenesis. Baseline differences in testicular histomorphology and testosterone metabolism between East Asian and Caucasian men have been reported, but whether this contributes significantly to varying degrees of sperm suppression in response to exogenous testosterone therapy is less known. Testosterone alone male hormonal contraceptive regimens are effective and applicable for East Asian men, and less so for Caucasians. Combinations of progestins with androgens are sufficient to optimize effectiveness of suppression and applicability to all ethnicities. New compounds such as steroidal or non-steroidal selective androgen receptor modulators with dual androgenic and progestational activities are potential compounds for further development as male hormonal contraceptive methods. At the present time, combined androgen and progestin contraceptive regimens appear to be effective, safe, reversible and convenient to use for all men with ethnic, cultural and environmental differences. Further refinements on the hormonal agent, methods of delivery, and dose optimization of the androgen relative to the progestin are necessary. This goal mandates further investment and large clinical trials in multiethnic populations to better define safety and efficacy.

Advances in male hormonal contraception

There is a need to develop new contraceptives, particularly for men whose current choices are suboptimal in terms of effectiveness and ease of reversibility. Recent surveys indicate that men and their partners would be willing to rely on male hormonal contraceptives. Male hormonal contraception works by reversibly suppressing sperm production. Testosterone in combination with progestins or gonadotropin-releasing hormone antagonists induces profound and consistent sperm suppression. Asian men are more susceptible to the suppressive effects of testosterone given alone, even if they may benefit from the addition of an adjunctive agent to obtain optimal contraceptive protection. The aim of this review is to comment on the recent relevant achievements in the field.

The acceptability of an injectable, once-a-month male contraceptive in China

Purpose An acceptability study of an injectable preparation of the synthetic steroid testosterone undecanoate as a once-a-month male contraceptive method was carried out concurrently with, but independently from, a clinical safety and efficacy trial of this preparation in China, from 1997 to 1999. Method Three hundred eight men, the entire group of volunteers enrolled in the clinical trial, were interviewed using a structured questionnaire. In addition, 24 sessions of focus group discussions and 54 in-depth interviews were conducted with a broad range of stakeholders, including men enrolled in the trial and their wives, potential users, service providers, principal investigators of the six participating clinical trial centers, provincial and national policy makers, and experts engaged in research and development of male methods of contraception. Results Overall, men found the regimen to be acceptable, and most reported no change or an improvement in their well-being as a result of participating in the clinical study. The frequency of the injections, monthly semen analyses and the need to use another contraceptive method during the period of sperm suppression were reported inconveniences of the trial. Conclusion Further research is needed to assess the long-term safety, continuation rates, satisfaction among users and issues related to service delivery.

Norethisterone Enanthate Plus Testosterone Undecanoate for Male Contraception: Effects of Various Injection Intervals on Spermatogenesis, Reproductive Hormones, Testis, and Prostate

The goal of this study was to find the most favorable injection interval of norethisterone enanthate (NETE) plus testosterone undecanoate (TU) in terms of gonadotropin, sperm suppression, and prostatic effects. Fifty normal men were randomly assigned to receive NETE 200 mg plus TU 1000 mg every 8 wk (n = 10), every 12 wk (n = 10), every 6 wk for 12 wk and then every 12 wk (n = 10), and every 6 wk for 12 wk and thereafter TU 1000 mg plus placebo every 12 wk (n = 10), and placebo plus placebo every 6 wk for 12 wk and then every 12 wk (n = 10) for 48 wk. Semen analyses, blood drawings, physical examinations, and prostate ultrasounds were performed throughout the study. Of the men in the 8-wk injection group, 90% (nine of 10) achieved azoospermia, compared with 37.5% (three of eight) in the 12-wk injection group (P = 0.019). TU plus placebo injected every 12 wk did not maintain sperm suppression. Prostate volumes did not change significantly in either group. In conclusion, these data suggest that the combined administration of NETE and TU at 8-wk intervals represents an effective hormonal contraceptive regimen.

Contraceptive Efficacy of a Depot Progestin and Androgen Combination in Men

Turner, Leo; Conway, Ann J.; Jimenez, Mark; Liu, Peter Y.; Forbes, Elise; McLachlan, Robert I.; Handelsman, David J.

Relationship between serum gonadotropins and spermatogenic suppression in men undergoing steroidal contraceptive treatment.

This study aimed to establish whether the degree of suppression of serum FSH and LH was related to sperm concentration in three testosterone (T) plus progestin contraceptive regimens. We measured serum FSH and LH using a modified, highly sensitive immunofluorometric assay in samples obtained from three published studies using T enanthate (TE; 100 and 200 mg weekly) plus daily oral doses of cyproterone acetate (CPA; 5-100 mg), levonogestrel (LNG; 150-500 micro g), or desogestrel (DSG; 150-300 micro g). Overall, men with sperm concentrations below 0.1 million/ml had significantly lower gonadotropin levels (serum FSH, approximately 0.12 IU/liter; serum LH, approximately 0.05 IU/liter) than oligospermic men (sperm concentrations, 0.1-5 million/ml; serum FSH, 0.23-0.5 IU/liter; serum LH, 0.05-0.56 IU/liter), but the relationship was weak, indicating the possible existence of other determinants. Multivariate logistic regression was used to identify the influence of candidate predictors of spermatogenic effects of the T plus progestin regimens. In the LNG and DSG studies, the marked suppression of serum LH to less than 5% of baseline values (<0.15 IU/liter) was a consistent and highly significant predictor of sperm concentration (reduced to 2-7% that seen at higher LH levels) and the likelihood of its suppression below 1 million/ml (a proposed threshold for contraceptive efficacy). Serum FSH was not a significant independent predictor. The use of DSG and CPA (but not LNG) was a significant independent predictor of sperm suppression, and regimens that contained 200 mg TE weekly caused less spermatogenic suppression than 100 mg TE weekly. These findings suggest that T-progestin contraceptive regimens suppress sperm concentration by gonadotropin-dependent and -independent mechanisms. The suppression of serum LH is a major predictor of the suppression of sperm concentration suppression in the LNG and DSG treatment studies. On the other hand, the greater spermatogenic suppression in regimens containing DSG or CPA suggests that these progestins have additional actions to suppress spermatogenesis via a gonadotropin-independent mechanism(s)

Use of progestins in male contraception

Hormonal male contraception aims at suppression of spermatogenesis to azoospermia or at least to severe oligoasthenozoospermia, incompatible with the ability to induce a pregnancy. The general principle of this approach is based on interference with the endocrine regulation of spermatogenesis, i.e. the suppression of gonadotropins. Since both FSH (through the Sertoli cell) and LH (through the Leydig cell and testosterone (T)) are required for normal spermatogenesis, both gonadotropins need to be suppressed as strongly as possible. In East Asian men this can be achieved with T alone (preferably in depot preparations such as T undecanoate) but only two-thirds of Caucasian men respond with adequate sperm suppression. Therefore, in Caucasian men additional substances such as GnRH antagonists or progestins are required to suppress the pituitary. Over the past 30 years many combinations of various T preparations with different progestins have been tested in clinical trials. Since self-applicable steroid combinations (e.g. oral levonorgestrel or desogestrel with transdermal T) showed low effectiveness, currently injections and implants are under clinical development. Long-acting intramuscular T esters (e.g. T undecanoate), T pellets or implants (e.g. MENT) are combined with injections of DMPA or noresthisterone enanthate or with implants containing levonorgestrel or etonogestrel. Acute side-effects of these combinations appear to be minimal and tolerable, long-term effects need to be investigated.

Higher Testosterone Dose Impairs Sperm Suppression Induced by a Combined Androgen‐Progestin Regimen

In this study we compared the effects of high-dose and low-dose testosterone enanthate (TE) administered with the same dose of cyproterone acetate (CPA). Eighteen men aged 21-45 were treated with CPA 5 mg/day and with TE 100 mg/week (n = 9; CPA-5-100) or TE 200 mg/week (n = 9; CPA-5-200) for 16 weeks. Semen analyses were performed every 2 weeks; physical examination and chemistry, hematology, gonadotropin, and testosterone measurements were performed every 4 weeks. At week 16 of treatment, sperm counts were significantly more suppressed in the CPA-5-100 group than in the CPA-5-200 group. Sperm counts returned to baseline in all subjects after hormone administration ceased. No difference in gonadotropin levels was found at any time between the 2 groups. During the treatment phase, testosterone levels were significantly higher in the CPA-5-200 group than in the CPA-5-100 group. The present study confirms that CPA/TE administration induces profound sperm suppression. An increase in the dose of androgen resulted in less profound sperm suppression despite no difference in gonadotropin suppression. These data suggest that high testosterone levels can maintain sperm production in men.

Levonorgestrel Implants (Norplant II) for Male Contraception Clinical Trials: Combination with Transdermal and Injectable Testosterone

Recent studies demonstrate that combinations of androgens and progestagens are highly effective in the suppression of spermatogenesis in normal volunteers. To test whether progestagen and androgen delivery systems designed to produce steady serum levels will be as effective as other androgen plus progestagen combinations, we compared Norplant II and testosterone (T) transdermal patch to T patch alone on the suppression of spermatogenesis in normal men. Thirty-nine healthy male volunteers (age, 20–45 yr) were randomly assigned to one of two groups. Group 1 (n = 19) received two transdermal T patches daily (Testoderm TTS, each patch designed to deliver about 5 mg/d T) alone, and group 2 (n = 20) received combined Norplant II [Jadelle, four capsules delivering ∼160 μg/d levonorgestrel (LNG)] plus T patch. Neither of these regimens were very effective, with suppression of spermatogenesis to severe oligozoospermia occurring in less than 60% of subjects. We then expanded the study to include two more groups to determine whether T patch or Norplant II was the main factor causing the inadequate suppression of spermatogenesis. Another 29 subjects were randomized to one of two groups. Group 3 (n = 15) received oral LNG (125 μg/d) plus T patch, and group 4 (n = 14) received Norplant II plus T enanthate (TE) injection (100 mg/wk im). After a pretreatment phase of 4 wk, all subjects received treatment for 24 wk, followed by a recovery period of 12–24 wk. Steady-state serum LNG levels (800–1200 pmol/liter) were achieved from wk 3–24 after Norplant II insertion and decreased rapidly after the removal of the implants at wk 24. Trough serum LNG levels after oral LNG administration were at a comparable range (940–1300 pmol/liter). Azoospermia was achieved in 24%, 35%, 33%, and 93%, and severe oligozoospermia (<1 × 106/ml) developed in 24%, 60%, 42%, and 100% of the subjects in groups 1, 2, 3, and 4, respectively, during treatment phase. All subjects in the Norplant II plus TE groups had persistent sperm concentrations less than 3 × 106/ml from wk 12 until the end of treatment. Concomitant with the marked suppression of spermatogenesis in the Norplant II plus TE group, serum FSH and LH levels were most decreased in this group compared with all other groups. In the T patch-only group, serum SHBG was not suppressed, and total serum T was higher than baseline levels. In the other three groups administered progestagens, serum SHBGs were significantly suppressed, and serum total T remained similar to baseline levels. Serum free T levels were not changed in any group. Except for a suppression of serum high-density lipoprotein cholesterol, there was no significant change in weight, hematocrit, clinical chemistry, or prostate-specific antigen levels in any of the treatment groups. Although more efficacious than T patch alone, Norplant II or oral LNG plus T patch was not as effective in suppressing spermatogenesis to severe oligo- or azoospermia as in previous reports using oral LNG plus TE. This relative lesser efficacy occurred despite the achievement of serum LNG levels by Norplant II that were equivalent to those reported after administration of oral LNG. Substituting the transdermal T delivery system with TE injections resulted in very effective suppression of sperm output. The difference in spermatogenesis suppression of these combined regimens is likely due to less T delivered by the transdermal patch compared with the TE weekly injections. We conclude that Norplant II implants plus TE 100 mg/wk were very efficient in suppressing spermatogenesis to a level acceptable for contraceptive efficacy. This study demonstrates that the dose or route of administration of androgens is critical for sperm suppression in combined androgen-progestagen regimens for hormonal male contraception.

Variability in sperm suppression during testosterone administration to adult monkeys is related to follicle stimulating hormone suppression and not to intratesticular androgens.

Sex steroid-based male contraceptive regimens do not induce consistent azoospermia. The reason for this variable response is obscure. We used normal adult male monkeys, Macaca fascicularis (n = 9) as a model of testosterone (T)-induced gonadotropin suppression to understand the basis for variability in spermatogenic suppression during hormonal contraception. As observed in men, T administration to these monkeys induced azoospermia in some animals and variable degrees of spermatogenic suppression in others. Based on their sperm counts, we divided these animals into two groups: azoospermic (azoo; n = 4) and nonazoospermic (nonazoo; n = 5) groups. Sperm density, testis volumes, and serum T, bioassayable LH (bioLH), immunoassayable FSH (immunoFSH), bioassayable FSH (bioFSH), and inhibin B were examined every 2 wk during the control period, 20 wk of T administration using SILASTIC brand (Dow Corning Corp.) implants, and recovery. Testes were biopsied for estimation of intratesticular T, dihydrotestosterone, and 5alpha-androstane-3alpha,17beta-diol. Serum T levels increased 1.5- to 2-fold, leading to decreased bioLH levels (48% of control) and intratesticular T levels (15% of control); neither LH nor intratesticular T levels differed between the azoo and nonazoo groups. In contrast, serum levels of FSH, by both bio- and immunoassay, during T administration were significantly lower in the azoo than in the nonazoo group. These results suggest that the degree of suppression of spermatogenesis is closely related to the degree of suppression of FSH levels and not to the levels of intratesticular androgens or to serum LH. These results imply that FSH plays a key role in supporting spermatogenesis in monkeys in this experimental regimen and suggest that maximal suppression of FSH may be essential to ensure consistent azoospermia in men during hormonal contraception.