Effects of tamoxifen metabolites on fertility of male rat

The effects of chronic oral administration of tamoxifen citrate, at a dose of 0.4 mg/kg/day, were compared to those of subcutaneous (s.c) administration of tamoxifen citrate, 4-hydroxy tamoxifen, N-desmethyl tamoxifen and intermittent oral tamoxifen administration on the fertility of the male rat and its post reversal progeny. The fertility parameters of 120 day-treated male rat sires from all groups and post reversal male F1 progeny of tamoxifen-treated sires were assessed. Chronic tamoxifen treatment via oral or s.c. routes reduced the fertility of the male rat, weights of accessory sex glands, serum luteinizing hormone, and testosterone levels without altering potency or sperm counts. However, antifertility effects of s.c. treatment were comparatively more consistent than those of oral treatment. 4-hydroxy and N-desmethyl tamoxifen failed to produce significant antifertility effects in the male rat. The antifertility effects of intermittent oral treatment were more sustained than those of chronic oral tamoxifen treatment. It is inferred that hepatic metabolism of tamoxifen interferes with its antifertility effects via oral route and that the parameters affected by chronic oral exposure in the male sires are completely reversed in progeny ensuing after an adequate period of drug withdrawal.     

Investigations on the use of testosterone oenanthate as a male contraceptive agent

The effect of exogenous testosterone on male gonadal function was in vestigated by applying a practical dose schedule of weekly injections of testosterone enanthate. 7 healthy young males received 22 intramuscular injections of 250 mg testosterone enanthate once a week for a period of 21 weeks. Mean sperm counts were reduced from a pretreatment value of 73 million sperm/ml to below 3 million sperm/ml within 9 weeks of testosterone administration and remained so during the whole treatment period. A marked recovery of spermatogenesis did not occur before 13 weeks after testosterone withdrawal, when the mean sperm count rose to 63 million sperm/ml. Changes of the mean sperm motility and percentage of normal sperm morphology generally paralleled those of the mean sperm concentration, whereas the mean semen volume, libido, potency, and secondary sex characteristics remained unaffected. A consistently azoospermic semen was not developed by any individual. This and the fact that sperm counts in 3 out of 7 males still showed some depression of spermatogenesis at the end of the observation period of 28 weeks after testosterone withdrawal indicate that testosterone enanthate admin istered in the described dose schedule is not a safe male contraceptive agent. However, further research on the use of hormones for the control of fertility in men seems warranted.     

Reversible antifertility action of testosterone propionate in human males

Seven healthy male volunteers were injected intramuscularly with 25 mg/ day testosterone propionate for sixty days. Sperm counts and volume of semen were recorded at 15 day intervals. The subjects became azoospermic 60 days after the treatment. Sperm counts were restored to pre-treatment levels 150 days after the withdrawal of the treatment. During the period of testosterone administration and recovery, the quantity of semen did not show any variations. Libido and potentia of the subjects was also normal during the experimental period. This study suggests the possibility of using testosterone as an antifertility agent in human males.     

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use

BACKGROUND: This study was conducted to investigate the effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters. STUDY DESIGN: Thyroid and androgen parameters were measured in 59 women treated with a monophasic combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or according to an extended-cycle regimen (four extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle, or on Days 82-84 of the first and fourth extended cycle. RESULTS: At both time points, the serum concentrations of thyroxine-binding globulin were elevated by about 65% in both treatment regimens. Likewise, both groups showed an increase in total triiodothyronine (T3) and total thyroxine (T4) by 30-40%, and no change in free T4. Until the 12th month of conventional treatment, the level of free T3 remained unchanged but decreased slightly during the extended-cycle regimen. In both groups there was a rise of sex hormone-binding globulin by 210-230% after 3 months and by 220-250% after 12 months. The levels of total testosterone were reduced by about 40% and those of free testosterone by 55-65% after 3 and 12 months. CONCLUSION: The results suggest that, during conventional and extended-cycle treatment with EE/DNG, a steady state in the effects on thyroid hormones and androgen parameters was reached within 3 months and that the changes in the various hormonal parameters did not substantially differ between conventional and extended-cycle regimen.     

Changes in the concentrations of testosterone, luteinising hormone and progesterone associated with administration of embelin.

The mode of action of embelin, a naturally occurring plant benzoquinone with male fertility regulating potential, was investigated. Sexually mature white New Zealand male rabbits were injected intra-muscularly with embelin (30 mg/kg body wt) on alternate days for 14 days (7 injections). Blood was collected on alternate days over 27-day period from the beginning of embelin administration. Testosterone and progesterone levels were measured by radioimmunoassay and luteinising hormone (LH) by mouse interstitial cell testosterone bioassay. There was a marked reduction of testosterone concentrations within two days of embelin administration and up to 90% reduction by the 6th day. LH showed a corresponding rise with the falling testosterone levels. Similarly, there was rapid increase in progesterone levels with the administration of embelin. Both the concentrations of progesterone and LH declined when embelin dosage was stopped. Evidence from the observed changes in the levels of the three hormones suggest that embelin disrupts production of testosterone at the testicular level.     

Effect of two oral contraceptives containing 30 μg ethinylestradiol and 75 μg gestodene or 150 μg desogestrel upon various hormonal parameters

The effect of two oral contraceptives containing 30 μg ethinylestradiol + 75 μg gestodene or 30 μg ethinylestradiol + 150 μg desogestrel upon various hormonal parameters were measured in 11 women each on days 1, 10, and 21 of the first, second, third, sixth, and twelfth treatment cycle and compared to the levels on days 1, 10, and 21 of the preceding control cycle.

There was no significant difference in the clinical effects or in the influence on the serum hormone parameters between both formulations. A significant decrease in the serum concentrations of luteinizing hormone and follicle stimulating hormone was observed during each cycle which was dependent on the duration of intake. Contrary to this, prolactin was not significantly altered, but 6 out of the 22 women showed episodically elevated prolactin levels. Serum estradiol and progesterone were profoundly suppressed, except one woman who ovulated during the twelfth cycle probably due to a therapy with metamizol, trimethoprim and sulfamethoxazole.

The concentrations of dehydroepiandrosterone-sulphate were significantly and time-dependently reduced by 20 to 25% during each treatment cycle.

There was also a significant decrease in the serum levels of testosterone by 20 to 30% and of free testosterone by 40 to 60%, while sex hormone-binding globulin increased by 250 to 300%.

It could be observed that during the pill-free interval of 7 days the pituitary and ovarian function recoverd, while the sex hormone-binding globulin levels remained elevated by 100%.     

Effect of four oral contraceptives on thyroid hormones,adrenal and blood pressure parameters

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on thyroid hormone parameters, cortisol, aldosterone, endothelin-1 and angiotensin II was investigated. Four groups composed of 25 volunteers each (ages between 18 and 35 years) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken by venipuncture after at least 12 h fasting on Day 21-26 of the control cycle and on Day 18-21 of the first, third and sixth treatment cycle. There was a significant increase in triiodothyronine (T3) and thyroxine (T4) by 20-40% in all treatment cycles, while thyroid-stimulating hormone was significantly increased only with EE/EV/DNG. Treatment with the DNG-containing OCs caused no change in free T4 (FT4) and a transitory reduction in free T3 (FT3) levels during the first cycle. During intake of EE/LNG, FT4 rose slightly, while FT3 was not altered. The pronounced rise in the serum concentrations of cortisol appeared to be related to the EE dose. During the first three cycles of treatment, no effect on angiotensin II levels was observed, while in the sixth cycle a significant decrease was measured in all treatment groups. The four OCs did not influence the serum concentrations of endothelin-1 and no consistent effects were found concerning those of aldosterone. The results suggest that the three DNG-containing and the LNG-containing low-dose OCs may increase T3, T4 and cortisol due to an elevated binding to serum globulins, while the free proportion of the hormones is not or only slightly changed. Therefore, these OCs have only minor effects on thyroid function, adrenal and blood pressure serum parameters.     

Estrogenic effect of yam ingestion in healthy postmenopausal women

OBJECTIVE: Yam (Dioscorea) has been used to treat menopausal symptom folklorically. This study was to investigate the effects of yam ingestion on lipids, antioxidant status, and sex hormones in postmenopausal women. METHODS: Twenty-four apparently healthy postmenopausal women were recruited to replace their staple food (rice for the most part) with 390 g of yam (Dioscorea alata) in 2 of 3 meals per day for 30 days and 22 completed the study. Fasting blood and first morning urine samples were collected before and after yam intervention for the analyses of blood lipids, sex hormones, urinary estrogen metabolites and oxidant stress biomarker. The design was a one arm, pre-post study. A similar study of postmenopausal women (n = 19) fed 240 g of sweet potato for 41 days was included as a control study. Serum levels of estrone, estradiol and SHBG were analyzed for this control group. RESULTS: After yam ingestion, there were significant increases in serum concentrations of estrone (26%), sex hormone binding globulin (SHBG) (9.5%), and near significant increase in estradiol (27%). No significant changes were observed in serum concentrations of dehydroepiandrosterone sulfate, androstenedione, testosterone, follicular stimulating hormone, and luteinizing hormone. Free androgen index estimated from the ratio of serum concentrations of total testosterone to SHBG decreased. Urinary concentrations of the genotoxic metabolite of estrogen, 16alpha-hydroxyestrone decreased significantly by 37%. Plasma cholesterol concentration decreased significantly by 5.9%. Lag time of low-density lipoprotein oxidation prolonged significantly by 5.8% and urinary isoprostane levels decreased significantly by 42%. For the control subjects fed with sweet potato, all three hormone parameters measured were not changed after intervention. CONCLUSION: Although the exact mechanism is not clear, replacing two thirds of staple food with yam for 30 days improves the status of sex hormones, lipids, and antioxidants. These effects might reduce the risk of breast cancer and cardiovascular diseases in postmenopausal women.     

铅和乙醇对雄性大鼠生殖系统的联合毒作用

采用整体动物实验方法,观察铅和乙醇对大鼠精子数量和质量,以及血中性激素水平的联合作用。结果显示,精子计数联合组比铅和乙醇单独作用组显著减少;精子活动度分析联合组与其他各组比较显著下降。铅和乙醇单独作用均可使雄性大鼠血清睾酮(T)升高,促黄体生成激素(LH)下降,联合作用使T降低,LH较单独作用组升高。提示铅和乙醇联合染毒对雄性大鼠生殖毒性影响可能具有增毒作用。     

Effects of chrysin on urinary testosterone levels in human males

The equilibrium of sexual hormones in both sexes is controlled in vertebrates by the enzyme aromatase, a member of the cytochrome P450 superfamily, which catalyzes the conversion of androstenedione and testosterone into estrone and estradiol, respectively. Flavonoids are diphenolic compounds present in whole grains, legumes, fruits, and vegetables that are strongly implicated as protective in coronary heart disease, stroke, and cancer. One flavonoid, chrysin, found in high concentrations in honey and propolis, has been shown to be an inhibitor of aromatase enzyme activity. These foods are often used as supplements, particulary by sportsmen for their energetic and antioxidant properties. The aim of this study was to verify if daily treatment for 21 days with propolis and honey, containing chrysin, would modify urinary concentrations of testosterone in volunteer male subjects. In fact, aromatase inhibition by chrysin could block the conversion of androgens into estrogens with a consequent increase of testosterone, eventually measurable in urine samples. The obtained data did not show alterations of the levels of testosterone in the volunteers after 7, 14, and 21 days of treatment in comparison with baseline values and compared with measurements on the control subjects at the same time. In conclusion, the use of these foods for 21 days at the doses usually taken as oral supplementation does not have effects on the equilibrium of testosterone in human males.     

Oral levo-norgestrel - testosterone effects on spermatogenesis, hormone levels, coagulation factors and lipoproteins in normal men

Four healthy men volunteered to be treated for eight to nine months with daily oral levo-norgestrel (250 micrograms) and oral testosterone (200-600 mg) as a possible contraceptive. This was followed by a recovery phase of 5-10 months. The oral steroid combination significantly decreased sperm count in 3 of 4 subjects, and significantly increased abnormal spermatozoa, serum LH was decreased during treatment but serum FSH remained constant, except for one volunteer. Serum testosterone was decreased except for 2 daily peaks associated with the oral testosterone. During the recovery period, sperm counts and morphology, serum testosterone and serum LH returned to normal, whereas serum FSH levels were increased. Platelet aggregability induced by ADP, increased in 3 volunteers during treatment as did fibrinolytic activity and fibrinolytic capacity (2 of 3 subjects). There was a reduction in the hepatic triglyceride lipase activity but no change was seen in serum triglycerides, serum cholesterol, serum LDL, serum HDL, peripheral lipoprotein lipase activity and the intravenous fat tolerance test. No other toxicological side effects were seen.     

Fluoride-induced disruption of reproductive hormones in men

Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.     

Estrogenic Effect of Yam Ingestion in Healthy Postmenopausal Women

Objective: Yam (Dioscorea) has been used to treat menopausal symptom folklorically. This study was to investigate the effects of yam ingestion on lipids, antioxidant status, and sex hormones in postmenopausal women.

Methods: Twenty-four apparently healthy postmenopausal women were recruited to replace their staple food (rice for the most part) with 390 g of yam (Dioscorea alata) in 2 of 3 meals per day for 30 days and 22 completed the study. Fasting blood and first morning urine samples were collected before and after yam intervention for the analyses of blood lipids, sex hormones, urinary estrogen metabolites and oxidant stress biomarker. The design was a one arm, pre-post study. A similar study of postmenopausal women (n = 19) fed 240 g of sweet potato for 41 days was included as a control study. Serum levels of estrone, estradiol and SHBG were analyzed for this control group.

Results: After yam ingestion, there were significant increases in serum concentrations of estrone (26%), sex hormone binding globulin (SHBG) (9.5%), and near significant increase in estradiol (27%). No significant changes were observed in serum concentrations of dehydroepiandrosterone sulfate, androstenedione, testosterone, follicular stimulating hormone, and luteinizing hormone. Free androgen index estimated from the ratio of serum concentrations of total testosterone to SHBG decreased. Urinary concentrations of the genotoxic metabolite of estrogen, 16α-hydroxyestrone decreased significantly by 37%. Plasma cholesterol concentration decreased significantly by 5.9%. Lag time of low-density lipoprotein oxidation prolonged significantly by 5.8% and urinary isoprostane levels decreased significantly by 42%. For the control subjects fed with sweet potato, all three hormone parameters measured were not changed after intervention.

Conclusion: Although the exact mechanism is not clear, replacing two thirds of staple food with yam for 30 days improves the status of sex hormones, lipids, and antioxidants. These effects might reduce the risk of breast cancer and cardiovascular diseases in postmenopausal women.     

来曲唑联合尿促性素用于排卵障碍患者促排卵效果观察

目的:比较来曲唑(LE)联合尿促性素(HMG)与他莫昔芬(TMX)联合HMG对排卵障碍患者的促排卵效果及其对生殖激素的影响。方法:拟行促排卵治疗的197例排卵障碍不孕症患者随机分实验LE+HMG组(105例、211周期)和对照TMX+HMG组(92例、201周期),实验组于月经周期第3～7天口服LE 5.0 mg/d共5天,第8天起肌注HMG 75～150U/d至HCG日;对照组于月经周期第5～9天口服TMX 10 mg,2次/d共5天,第10天起肌注HMG 75～150 U/d至HCG日。超声监测卵泡发育,并于月经周期第8天和HCG注射日取静脉血测定黄体生成素(LH)、雌二醇(E2)、睾酮(T);观察优势卵泡数、成熟卵泡数、排卵率、妊娠率、子宫内膜厚度、多胎妊娠率、卵巢过度刺激综合征(OHSS)发生率及生殖激素变化。结果:LE+HMG组的排卵率和周期妊娠率与TMX+HMG组相似(P>0.05),HCG日其优势卵泡数和成熟卵泡数均显著低于TMX+HMG组(P<0.05)。两组在HCG日子宫内膜的厚度无明显差异(P>0.05),其在月经周期第8天和HCG日的血清E2水平均显著低于TMX+HMG组(P<0.05),血清T水平及LH水平两组无明显差异(P>0.05)。LE+HMG组未发生1例OHSS及多胎妊娠。结论:LE+HMG用于排卵障碍的不孕症妇女具有良好的排卵率和周期妊娠率,且并发症低。     

A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic parameters: I. Effects upon sexual hormone levels

The effect of a low-dose triphasic oral contraceptive (OC) containing ethinyl estradiol and levonorgestrel (EE/NG) upon serum levels of endogenous sexual hormones was compared to that of a preparation containing EE and desogestrel (EE/DG). Blood samples were taken on Day 6, 11, 21, and 28 of a control cycle and of the third cycle of treatment with either the EE/NG or EE/DG preparation (11 volunteers each). After a washout period of 3 months, the contraceptives were changed in a cross-over fashion. Blood samples were again taken on Day 6, 11, 21, and 28 of the third washout cycle and the third treatment cycle.

There was no significant suppression of serum LH and FSH during treatment with EE/NG and EE/DG except on Day 21, while estradiol levels were significantly lowered. Similar to the gonadotropin concentrations, the estrogen levels showed great individual variations; although they were depressed in the majority of the women, there was a considerable stimulation of follicular activity in 36% of the women under EE/NG and 18% under EE/DG. Both EE/NG and EE/DG suppressed significantly serum progesterone, testosterone, and DHEA-S, while prolactin was unaffected.

In three cases an escape ovulation seemed to have occurred, but no pregnancy was observed. The spottings (8/22 women) and breakthrough bleedings (6/22 women) did not correlate with the serum levels of estradiol.

The results indicate that the suppression of gonadotropin secretion during treatment with low-dose OC is a time-dependent process which in some women may be at or below the threshold of safe ovulation inhibition.     

Effect of four different oral contraceptives on various sex hormones and serum-binding globulins

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on various hormone parameters and serum-binding globulins was investigated. Four groups with 25 volunteers each (18-35 years of age) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken after at least 12 h of fasting on Day 21-26 of the preceding control cycle and on Day 18-21 of the first, third and sixth treatment cycle. The serum concentrations of free testosterone were significantly decreased by about 40-60% in all four groups, while those of dehydroepiandrosterone sulfate (DHEAS) showed a time-dependent decrease during treatment. Except for EE/EV/DNG, which increased prolactin significantly during the third and sixth cycles, no change was observed with the EE-containing preparations. There was a significant increase in the levels of serum-binding globulins during treatment, which differed according to the composition of the OCs used. The rise in sex hormone-binding globulin (SHBG) was highest during intake of 30EE/DNG (+320%) and lowest with EE/LNG (+80%), while the effect of 20EE/DNG and EE/EV/DNG was similar (+270%). The thyroxine-binding globulin (TBG) levels increased significantly, by 50-60%, during treatment with the DNG-containing formulations, while the effect of EE/LNG was less significant (+30%). The rise in corticosteroid-binding globulin (CBG), which occurred in all groups, was most pronounced in women treated with 30EE/DNG (+90%) and least with EE/EV/DNG (+55%), indicating a strong influence of EE and no effect of the progestogen component. In all treatment groups, the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter. Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG. There was no significant change in blood pressure, body mass index or pulse rate throughout the study. In conclusion, the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation. The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE. In contrast to EE, the use of estradiol in OCs appeared to increase prolactin release, while the cycle control was better with the OC containing 30 microg EE.     

Semen quality and reproductive sex hormone levels in Peruvian pesticide sprayers

To determine the association between occupational pesticide exposure and semen quality among sprayers using organophosphate (OPs) pesticides, 31 pesticide sprayers and 80 men who were not exposed were studied. Semen and blood samples were obtained one day after last pesticide application. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, and fructose and zinc concentrations. Blood samples were analyzed for sex hormones. Pesticide sprayers had significantly reduced age-adjusted seminal volume, percentage of motility, percentage of sperm with normal morphology, serum luteinizing hormone, serum testosterone levels, and seminal zinc concentration (a marker of prostate function), as well as significantly increased time of liquefaction, seminal pH, percentage of immature sperm morphology, and leukocyte concentration. These findings provide further evidence that occupational exposures to OP pesticides adversely affect semen quality and sex hormones.     

Dynamics of the responses in secretion of luteinising hormone, leptin and insulin following an acute increase in nutrition in mature male sheep

In Merino rams, an increase in the plane of nutrition increases the frequency of luteinising hormone (LH) pulses within a few days and this response is correlated with changes in the circulating concentrations of metabolic hormones. To analyse early dynamic aspects of these responses, we studied mature rams fed with diets that contained either low or high amounts of energy and protein. Jugular blood was sampled every 20 min for 96 h, including a control period of 24 h before the change of diet in the high-diet group. In the high-diet group, a significant increase in LH pulse frequency was first detected 6 h after the increase in nutrition on Day 1 and the frequency remained significantly elevated throughout the 72-h treatment period, except for a 12-h period on Day 2. Following the change of diet, insulin concentrations increased within 3 h and leptin concentrations increased within 7 h, after which time the concentrations of both hormones remained high. Dietary treatment did not affect the concentrations of thyroxine or insulin-like growth factor-I, but the high diet increased the concentrations of tri-iodothyronine. These observations are consistent with insulin and leptin playing a role in the early activation of the gonadotrophin-releasing hormone-LH axis by nutritional inputs.     

Clinical evaluation of long-term treatment with levo-norgestrel and testosterone enanthate in normal men

Thirteen healthy men (25–35 years) with proven fertility were scheduled for long-term treatment (> 12 months) with levo-norgestrel (500 μg daily) and testosterone enanthate (200 mg monthly). The volunteers were regularly investigated prior to, during and after treatment. Seven volunteers withdrew from medication after 1 to 12 months of treatment; three due to psychological side effects, one because of stiffness of a finger joint, two for personal reasons and one for unspecified reasons. Sperm counts were significantly decreased during treatment and in 7 volunteers the sperm counts were <5 × 10⁶/ml. However, two of these volunteers exhibited a breakthrough in sperm counts after 12 and 13 months of a 16-month treatment period. Serum testosterone, serum LH and serum FSH were significantly decreased during treatment, but returned, as did sperm counts, to normal levels after withdrawal of treatment. No rebound effect was seen. Potency and libido remained unchanged. No toxicological side effects were observed and finally no consistent changes were seen in blood coagulation parameters.