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We studied whether long-term use of mesterolone (12 weeks and longer) changed the pattern of steroid metabolites in urine from male subjects. We noticed an increase in dehydroepiandrosterone (DHEA) levels from 211-4 +/- 130.5 ug/die to 9943.8 +/- 6564.7 ug/die in the urine of all subjects tested. This increase was significant. After mesterolone administration was discontinued, DHEA levels decreased to their initial value. DHEA levels showed the smallest increase in those subjects having high plasma FSH levels. Perhaps the delta 4 pathway of testosterone synthesis may be preferred in these three subjects. We suppose that mesterolone has a blocking effect on the delta 5 pathway of testosterone synthesis. DHEA from the DHEA-pool can be used for testosterone synthesis and mesterolone seems to block some enzymes in the synthetic pathway. We were not able to detect a decrease in plasma testosterone levels during mesterolone use because of technical problems. Moreover, our patients told us that they felt ill after discontinuing mesterolone use; it may be possible that there is a psychotropic DHEA-effect during mesterolone use.
Based on computer EEG (CEEG) profiles, in high doses, antidepressant properties of mesterolone, a synthetic androgen, were predicted. In a double-blind placebo controlled study, the clinical effects of 300-450 mg daily mesterolone were investigated in 52 relatively young (age range 26-53 years, mean 42.7 years) male depressed outpatients. During 6 weeks of mesterolone treatment, there was a significant improvement of depressive symptomatology. However, since an improvement was also established during the placebo treatment, no statistically appreciable difference in the therapeutic effects of mesterolone was established compared to placebo. Mesterolone treatment significantly decreased both plasma testosterone and protein bound testosterone levels. Patients with high testosterone levels prior to treatment seem to have had more benefit from mesterolone treatment than patients with low testosterone levels. The degree of improvement weakly correlated to the decrease of testosterone levels during mesterolone treatment.
A prospective randomized double-blind study was undertaken to assess the effect on male fertility of 6 months' treatment with the synthetic androgen mesterolone. The study was performed in seven centres and 248 infertile couples were recruited. All men and their partners were investigated according to the standardized WHO protocol--Investigation and Diagnosis of the Infertile Couple. Following this investigation, 157 couples were selected in whom the male diagnosis was primary idiopathic testicular failure or idiopathic low sperm motility; the female partner had no demonstrable cause for infertility or was under successful treatment for a minor endocrine problem. The remaining 91 couples admitted were either incompletely investigated or had some additional factor associated with infertility. Men received either 150 or 75 mg mesterolone daily or placebo. Response was assessed in terms of semen characteristics and the partner's pregnancy rate. The cumulative life table pregnancy rates among all couples 8 months after randomization were 9 +/- 3% (+/- standard error), 12 +/- 4% and 16 +/- 4% in the placebo, 75 and 150 mg mesterolone groups, respectively. The ratios of the pregnancy rates compared to placebo were 1.3 (0.5-3.2) and 1.8 (0.7-4.4) for the 75 and 150 mg mesterolone groups respectively. Among the subset of 157 couples satisfying the strict eligibility criteria, the pregnancy rates were 11 +/- 5%, 12 +/- 5% and 19 +/- 6% in the placebo, 75 and 150 mg mesterolone groups, respectively. The corresponding ratios of pregnancy rates to the placebo group were 1.2 (0.4-3.4) and 1.8 (0.6-5.3) for the 75 and 150 mg mesterolone groups respectively. There were no significant changes semen quality during the course of the study, apart from an increase in sperm concentration 3 months after the start of treatment. The increase was greatest among the placebo treated group, but did not differ significantly between treatment groups.
The possible effect of Mesterolone (Schering N.V., Brussels, Belgium) (1 alpha-methyl-5-alpha-androstane-17 beta-ol-3-one) on semen quality and fertility of men with idiopathic oligoasthenospermia and/or teratozoospermia has been evaluated in a double-blind trial. The study included 52 patients who were treated during 12 months with either 150 mg/d of Mesterolone or placebo. The overall pregnancy rate was similar in the Mesterolone-treated cases (26%) and in the placebo control cases (48%), although a significant increase in motility and in the proportion of spermatozoa with normal morphology was recorded in the Mesterolone-treated cases. Because similar semen improvement also occurred in the placebo controls, our findings cast doubt on the possible usefulness of high-dose Mesterolone treatment of idiopathic male infertility.
A psychopharmacological profile of mesterolone, an androgen and potential antidepressant drug, was tested in mice and rats. Given in a dose of 80 mg/kg ip, mesterolone potentiated the action of L-DOPA in mice and in doses 40 and 80 mg/kg ip potentiated the amphetamine stereotypy in rats. On the other hand, in doses of 20--80 mg/kg ip mesterolone did not affect the reserpine induced hypothermia and ptosis, did not antagonize the apomorphine induced hypothermia in mice, did not change the motor stimulation produced by amphetamine and did not affect the spiperone induced catalepsy in rats. Mesterolone did not affect the head twitch response after 5-hydroxytryptophan in mice and was inactive in the behavioral despair test in rats. The results indicate that the psychopharmacological profile of mesterolone only slightly resembles the profile of classical imipramine-like anti-depressants.
Two hundred fifty subfertile men with idiopathic oligospermia (count less than 20 million/ml) were treated with mesterolone (100-150 mg/day) for 12 months. Seminal analysis were assayed 3 times and serum follicle stimulating hormone (FSH) luteinizing hormone (LH) and plasma testosterone were assayed once before treatment and repeated at 3, 6, 9 and 12 months after the initiation of treatment. One hundred ten patients (44%) had normal serum FSH, LH and plasma testosterone, 85 patients (34%) had low serum FSH, LH and low plasma testosterone. One hundred seventy-five patients (70%) had moderate oligospermia (count 5 to less than 20 million/ml) and 75 patients (30%) had severe oligospermia (count less than 5 million/ml). Seventy-five moderately oligospermic patients showed significant improvement in the sperm density, total sperm count and motility following mesterolone therapy whereas only 12% showed improvement in the severe oligospermic group. Mesterolone had no depressing effect on low or normal serum FSH and LH levels but had depressing effect on 25% if the levels were elevated. There was no significant adverse effect on testosterone levels or on liver function. One hundred fifteen (46%) pregnancies resulted following the treatment, 9 of 115 (7.8%) aborted and 2 (1.7%) had ectopic pregnancy. Mesterolone was found to be more useful in patients with a sperm count ranging between 5 and 20 million/ml. Those with severe oligospermia (count less than 5 million) do not seem to benefit from this therapy.
New metabolites of mesterolone, methenolone and stenbolone bearing a C18 hydroxyl group were isolated from the steroid glucuronide fraction of urine specimens collected after administration of single 50 mg doses of these steroids to human subjects. Mesterolone gave rise to four metabolites which were identified by gas chromatography/mass spectrometry as 18-hydroxy-1 alpha-methyl-5 alpha-androstan-3,17-dione 1, 3 alpha,18-dihydroxy-1 alpha-methyl-5 alpha-androstan-17-one 2, 3 beta,18-dihydroxy-1-alpha-methyl-5 alpha-androstan-17-one 3 and 3 alpha,6 xi,18-trihydroxy-1 alpha-methyl-5 alpha-androstan-17-one 4. These data suggest that mesterolone itself was not hydroxylated at C18, but rather 1 alpha-methyl-5 alpha-androstan-3,17-dione, an intermediate metabolite which results from oxidation of mesterolone 17-hydroxyl group. In addition to hydroxylation at C18, reduction of the 3-keto group and further hydroxylation at C6 were other reactions that led to the formation of these metabolites. It is of interest to note that in the case of both methenolone and stenbolone, only one 18-hydroxylated urinary metabolite namely 18-hydroxy-1-methyl-5 alpha-androst-1-ene-3,17-dione 5 and 18-hydroxy-1-methyl-5 alpha-androst-1-ene-3,17-dione 6 were both detected in post-administration urine specimens. These data indicate that the presence of a methyl group at the C1 or C2 positions in the steroids studied is a structural feature that seems to favor interaction of hepatic 18-hydroxylases with these steroids. These data provide further evidence that 18-hydroxylation of endogenous steroids can also occur in extra-adrenal sites in man.
Fifty-nine carefully selected oligozoospermic men were randomly treated with mesterolone (75 mg/day) or placebo to improve fertility. After 6 months the medication was changed from mesterolone to placebo or vice versa. Fourteen pregnancies occurred, 7 under mesterolone and 7 under placebo. A testicular biopsy score was of prognostic value: the men who impregnated their partner had a significantly higher mean score than the men who did not fertilize. No other significant differences between these two groups of men were observed. Mesterolone had no significant influence other than placebo.
Forty subfertile men with idiopathic oligospermia were randomly treated with mesterolone or with placebo for more than 4 months. Seminal analysis was performed thrice before treatment, and twice after 16 weeks of treatment. There was a significant increase of semen volume (P less than .05), mean sperm concentration (P less than .01), and mean total sperm count per ejaculate (P less than .01) with mesterolone therapy. Sperm motility and morphological characteristics were not modified by mesterolone therapy. Mesterolone was found to be effective in improving the sperm concentration in mild and moderate rather than in severe idiopathic oligospermia.
The response to Mesterolone, in doses of 25 mg/day, was examined in 42 pathospermic patients. Treatment lasted for 100 days. The pronounced response to the Mesterolone treatment was observed in hypozoo- and oligozoospermia with low initial fructose content in the ejaculate. Fructose content attained its normal range after the treatment. During the therapeutic period 11 wives became pregnant. The authors conclude that Mesterolone does not influence plasma FSH, LH and testosterone levels, it has only peripheral effects.
A double-blind clinical study of 30 boys, six to ten years of age, with primary nocturnal enuresis was undertaken to assess the role of androgens in treating enuresis. The oral synthetic androgen mesterolone was selected because of its minimal potential toxic effects. Twenty boys were treated with mesterolone and 10 received placebo. Fourteen boys (70%) became dry during treatment (20 mg daily for 14 days), and 5 (25%) remained dry for a follow-up period of four months. Increased cystometric bladder capacity and disappearance of uninhibited detrusor contractions were noticed in a significant number of cases after treatment. No side effects were recorded. Mesterolone has probably modulated the autonomic innervation of the vesical musculature with correction of the defective neural mechanism which is believed to be implicated in the pathogenesis of nocturnal enuresis.
Mesterolone, 150 mg daily by mouth, was given to 26 patients (10 men, 16 women) with renal anaemia on chronic haemodialysis (3 times for 5 hours). At the beginning of treatment the patients had been dialysed for at least 6 months under stable conditions: iron deficiency had been excluded or treated. Progressive improvement in the anaemia was observed during the treatment period. After 39 months the haemoglobin concentration had risen from 74 +/- 4 g/l to 95 +/- 5 g/l, haematocrit from 0.22 +/- 0.01 to 0.28 +/- 0.02, and the red-cell count from 2.44 +/- 0.12 X 10(12)/l to 3.09 +/- 0.2 X 10(12)/l. Side effects were rare; some patients developed increased appetite with a rise in body weight, while some women developed acne or hirsutism. There was no effect of mesterolone on liver function. The results indicate that mesterolone can favourably influence renal anaemia and that the side effects of this testosterone derivative are not such as to prohibit its use in women.
1. We describe a patient who developed deep vein thrombosis after commencing treatment with the synthetic androgen, mesterolone (Pro-Viron). 2. To investigate the potential thrombogenic action of this drug, a 21 day course of mesterolone (100 mg/day) was given to nine healthy male volunteers. 3. No significant change after treatment occurred in any of the blood tests performed (clotting times, Factor VIII coagulant activity, Factor VIII related antigen, antithrombin III activity, fibrinogen, fibrinogen-fibrin degradation products, plasminogen, euglobulin lysis time, urokinase sensitivity, platelet count, haematocrit, whole blood viscosity and plasma viscosity). 4. We conclude that in a conventional dose taken for 3 weeks mesterolone does not produce a consistent measurable prothrombotic state, nor does it enhance fibrinolysis.
Hormone levels were measured in patients with Klinefelter's syndrome after treatment with 100 mg mesterolone cipionate (twice monthly). There was no difference in plasma testosterone and FSH levels in treated and untreated patients. The basal and maximum LH levels were lower, but remained raised. The urinary excretion of testosterone as measured by liquid gaschromatography was higher in treated patients after treatment was discontinued.-From these results it is concluded that in spite of reported decreases of plasma testosterone during therapy with mesterolone cipionate this drug does not lead to severe impairment of the endogenous hormone production after discontinuing treatment.
Before including the detection of the methyl-5 alpha-dihydrotestosterones mesterolone (1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) and drostanolone (2 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) in doping control procedures, their urinary metabolites were characterized by gas chromatography/mass spectrometry. Several metabolites were found after enzymatic hydrolysis and conversion of the respective metabolites to their trimethylsilyl-enol-trimethylsilyl ether derivatives. The major metabolites of mesterolone and drostanolone were identified as 1 alpha-methyl-androsterone and 2 alpha-methyl-androsterone, respectively. The parent compounds and the intermediate 3 alpha,17 beta-dihydroxysteroid metabolites were detected as well. The reduction into the corresponding 3 beta-hydroxysteroids was a minor metabolic pathway. All metabolites were found to be conjugated to glucuronic acid.
Forty-six subfertile men with idiopathic oligospermia were randomly assigned to 6 months of treatment with a placebo, clomiphene citrate (25 or 50 mg/day), mesterolone (100 mg/day), or pentoxifylline (1200 mg/day) or 4 months of testosterone enanthate treatment (100 or 250 mg on alternate weeks). Treatment with the placebo, mesterolone, pentoxifylline, and testosterone rebound therapy did not result in a significant increase in the mean sperm concentration or pregnancy in the partners. Clomiphene citrate at both dosages significantly increased the mean sperm concentration without improving sperm motility or morphology during the 6-month treatment period. Pregnancy rates of 36.4% and 22.2% were observed in partners of men receiving clomiphene citrate 25 mg/day and 50 mg/day, respectively. This study also illustrates the difficulties in identifying suitable patients for and assessing the efficacy of different treatment regimens.
There were no changes in plasma cholesterol, triglycerides, FSH and testosterone levels of 24 healthy men treated with mesterolone for infertility during period of 6 months. The patients were normolipemic and the daily doses were 75 mg. No side-effects were noticed. Mesterolone seems to have too selective or too low androgenic effect with the doses used in order to have an influence on the lipid metabolism of men.