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At least 19 recordsLinked to original sources

Assessment of the therapeutic effect of epimestrol and epimestrol associated with clomiphene in female sterility.

In 24 women with disturbances of ovulation treated for sterility with Epimestrol, ovulation was achieved in 3 patients but none of these became pregnant after therapy. Since it has been suggested that the association of Clomiphene with a weak estrogen might improve the pregnancy rate, we decided to administer Clomiphene associated with Epimestrol. Using this combined therapy in 58 patients, 32 out of the 58 women ovulated and 17 conceived. The overall rate of pregnancy using the combined therapy was no better than that obtained when Clomiphene alone is administered. From this study it is concluded that: (1) Epimestrol is not an effective method for the induction of ovulation, and (2) addition of Epimestrol to Clomiphene is of no clinical benefit.

Clomiphene

Epimestrol in treatment of inadequate luteal progesterone secretion.

Seventeen infertile normoprolactinemic women with luteal phase defects were treated with epimestrol. In ten patients, normalization of the impaired luteal phase was achieved. Under epimestrol treatment, periovulatory estradiol concentrations (1077.3 +/- 121.5 pmoles/liter versus 612.7 +/- 64.2 pmoles/liter; mean +/- SEM; P < 0.01) and cervical scores (10.8 +/- 0.3 versus 7.9 +/- 0.38; mean +/- SEM; P < 0.01) were improved, and luteal progesterone (60.0 +/- 9.1 nmoles/liter versus 19.98 +/- 3.14 nmoles/liter; mean +/- SEM; P < 0.001) and estradiol secretioon (813.1 +/- 101.1 pmoles/liter versus 581.9 +/- 73.7 pmoles/liter; mean +/- SEM; P < 0.05) were significantly increased in those women with normalization of the luteal phase as compared with the seven patients in whom epimesterol was without effect. Prolactin levels were elevated in all patients after epimestrol therapy (P < 0.05). Basal LH levels and LH-RH stimulated levels improved following administration of epimestrol (P < 0.01) in the 10 women with normal luteal phases. FSH levels were not significantly affected. Two patients became pregnant. No side effects were noted.

Adult

[Epimestrol in the treatment of normoprolactinemic corpus-lutem deficiency (author's transl)].

The treatment of normoprolactinemic corpus-luteum deficiency with epimestrol is reported. This is a frequent cause of infertility. The clinical and hormonal parameters for the diagnosis and follow-up evaluation of the treatment are described. In the present series 10 of 17 patients with primary infertility and normoprolactinemic corpus-luteum deficiency showed a normalization of the luteal phase. Two pregnancies occured following one cycle of treatment with epimestrol at 5 mg. daily from day 3 to day 12 of the cycle. Epimestrol shows no anti-estrogenic properties in contra-distinction to other ovulation stimulating drugs. The quality of the cervical secretion is therefore not impaired by epimestrol. Side effects or ovarian cysts were not observed.

Adult

[Action of epimestrol on pituitary thymidine kinase and gonadotropins in the rat. Comparison with clomiphene and cyclofenil (author's transl)].

The authors have evaluated the influence of epimestrol on several parameters: pituitary thymidine kinase in immature male rats, FSH and LH contents of pituitary and plasma in immature male and mature female rats, oestrous cycle of female rats. The results are compared with those obtained with clomiphene and cyclofenil. Epimestrol, as well as clomiphene, although at a lesser degree modifies gonadotropins levels; in contrast to clomiphene, in the pituitary thymidine kinase test epimestrol shows an oestrogenic potency but not an anti-oestrogenic one. More over it induces a vaginal cells cornification. These data suggest that epimestrol could be efficient in inducing pregnancy.

Animals

A comparative study of clomiphene and epimestrol on plasma progesterone, CBG, TBG and SHBG, and salivary progesterone levels.

The plasma levels of CBG, TBG, SHBG and progesterone, and salivary progesterone levels were measured in eight young ovulatory volunteers. After the control cycle four subjects received 50 mg/day of Clomiphene from days 5 to 9 of the first treatment cycle, and 10 mg/day of Epimestrol from days 5 to 15 of the second treatment cycle. The other four subjects received the treatments in reverse order. Between the two treatments there was one cycle without medication as a "wash-out" period. Plasma and saliva samples were obtained on days +6, +8 and +10 (day of LH peak was denoted by 0), always between 08.00 and 09.00 h. Statistical evaluation was done by means of an analysis of variance (ANOVA), and correlation coefficients were also calculated. Evaluation of data on effects of Clomiphene and Epimestrol on the plasma levels of CBG and salivary progesterone showed that Clomiphene induced a highly significant rise (p less than 0.001) in the CBG levels and decrease (p less than 0.001) in salivary progesterone levels, while no changes were seen following administration of Epimestrol. Both Clomiphene and Epimestrol treatments led towards higher plasma progesterone levels, those following Clomiphene administration being higher. Neither treatment induced significant changes in TBG or SHBG levels. It is concluded that Clomiphene induces significant elevations of CBG and decrease in salivary progesterone, which is thought to reflect the free progesterone fraction and may have significance in relation to a discrepancy between the ovulation and pregnancy rates following Clomiphene therapy.

Adult

[Comparative clinical studies on clomiphen, cyclofenil and epimestrol (author's transl)].

Report on the treatment of 310 anovulatory woment in 1173 treatment cycles with Clomiphen, Cyclofenil and Epimestrol. 63% of the patients had a biphasic basal body temperature record after treatment in 718 cycles. Patients with secondary amenorrhea of the first or the second degree had a satisfactory ovulation rate in 71% of the cases only by treatment with Clomiphen. In women with anovulatory cycles an overall ovulation rate of 75% was observed with all three medications. In 73 patients 78 pregnancies occurred. Of these, 38 pregnancies followed Cyclofenil, 25 pregnancies followed Clomiphen and 15 pregnancies followed Epimestrol corresponding to a 15%, 17% and 13% rate in the treated patients. 22 of these pregnancies ended in incomplete abortion. The side effects of Clomiphen especially visual and cystic ovarian and vasomotor side effects are more pronounced than the side effects of Cyclofenil and Epimestrol. The statistical analysis of the clinical results showed that Clomiphen and Cyclofenil had a higher rate of ovulation in secondary amenorrhea of the first or second degree than Epimestrol.

Amenorrhea

Induction of ovulation with epimestrol and luteinizing hormone-releasing hormone (LH-RH).

Luteinizing hormone-releasing hormone (LH-RH) was used to induce LH surge and ovulation in 20 patients in whom follicular maturation was provoked by epimestrol, used in a dose of 5 mg/day from the fifth to 14th day of the cycle. Patients with elevated prolactin levels and galactorrhea were not included in the study. Complete follicular maturation, as inferred by estradiol levels above 200 pg/ml, were observed in 13 of 20 patients following epimestrol treatment. LH-RH induced ovulation in 90% of these patients following a three-day course of treatment. Normal corpus luteum function with progesterone levels above 8 ng/ml was observed in most cases. Five pregnancies occurred in the first two cycles of treatment. In patients with low estradiol levels, following epimestrol priming, the administration of LH-RH did not result in ovulation.

Anovulation

Effect of epimestrol on gonadotropin and prolactin plasma levels and response to luteinizing hormone-releasing hormone/thyrotropin-releasing hormone in secondary amenorrhea and oligomenorrhea.

The effects of epimestrol (5 mg every 6 hours for 5 days) on basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), estradiol, progesterone, and dehydroepiandrosterone sulfate, and on the response to LH-releasing hormone (LH-RH) and thyrotropin-releasing hormone (TRH) stimulation, were studied in 18 cases of secondary amenorrhea and oligomenorrhea of hypothalamic-pituitary origin, in three cases of anorexia nervosa, in two cases of long-lasting progestin-induced amenorrhea, and in one case of precocious menopause. The results in the first 18 patients indicate that epimestrol treatment induces a significant increase in LH and Prl levels after 24 hours, while the FSH increase becomes significant only after 4 days of therapy. Twelve hours after discontinuation of treatment, all three hormone levels decreased significantly to values similar to the basal levels, while the pituitary response to LH-RH indicated a much more marked LH secretion than before treatment. A second test, performed 36 hours after the last drug administration, again showed a significantly higher LH response than that found under basal conditions. No significant variations were observed in the FSH response to LH-RH, nor in the Prl response to TRH. These data suggest that epimestrol interferes at the level of the centers responsible for Prl and gonadotropin secretion in the manner of a weak estrogen.

Adolescent

[Treatment of infertile women with epimestrol (author's transl)].

155 patients have been treated with epimestrol during 593 menstrual cycles in a daily dosage of 5, 10 or 2.5 mg from the 1st to the 10th or from the 5th to the 14th day of the cycle. 143 patients with secondary amenorrhoea, anovulatory cycles, ovulatory oligomenorrhoea, corpus luteum insufficiency, and normal cycles received epimestrol after an average period of 2.4 years of involuntary infertility. The pregnancy rate was 21% (n = 30), the spontaneous abortion rate 13% (n = 4). Twelve further patients not seeking pregnancy were treated with epimestrol because of secondary amenorrhoea and (or) anovulatory bleeding. The results were as follows: 1) In eugonadotropic secondary amenorrhoea 8 out of 12 patients ovulated, 5 out of 10 patients wanting children became pregnant. No patient with hypogonadotropism ovulated. 2) Out of 25 patients with anovulatory cycles or bleeding 13 ovulated and 4 became pregnant. 3) 17 out of 68 oligomenorrhoeic patients became pregnant. 4) In 12 out of 24 patients with corpus luteum insufficiency the hyperthermic phase improved and four patients became pregnant. 5) In 12 patients without anomalous cycles these remained unchanged and there were no pregnancies. 6) No side effects could be observed.

Abortion, Spontaneous

[Epimestrol in childless marriages (author's transl)].

In a gynaecological practice 49 patients were treated for primary or secondary infertility with epimestrol between January 1977 and June 1979. The selected group all had normogonadotropic, normoprolactinaemic anovulatory cycles (group II of the WHO scientific group 1976). Therapeutic measures extended over a total of 176 cycles in which 5 mg epimestrol (1 tablet Stimovul) were prescribed from the 5th to the 14th day. This procedure led to at least one ovulation in 86% of the cases and to pregnancy in 30 of the women. 23 pregnancies were without major complications. The abortion rate was 23%. Side effects of epimestrol treatment were only seen in occasional cases and only at the beginning of treatment.

Abortion, Spontaneous

Placebo-controlled study of effects of epimestrol on the pituitary-testicular axis in normal men.

Twenty healthy male volunteers were randomly allocated to the treatment with either 15 mg/day of epimestrol or placebo for 10 days. The plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), oestradiol (E2) and prolactin (PRL) were measured before, during and 4 days after the medication by radioimmunoassays. Data were statistically evaluated by means of an analysis of covariance. Circulating LH and FSH, and also T and E2 significantly increased in the epimestrol treated subjects. In the placebo treated subjects no significant changes in the plasma hormone levels were observed. There were no significant changes in the plasma levels of PRL in either group.

Administration, Oral

Bromocryptin and epimestrol in MAP-negative secondary amenorrheas.

18 patients, between 18 and 24 years of age, affected by normoprolactinemic secondary amenorrhea and still MAP-negative after three successive Epimestrol cycles underwent five cycles of a combined treatment (Bromocryptin and Epimestrol). Before and after the first cycle of combined treatment, in all patients FSH, LH, E2 and PRL were measured. Progesterone was evaluated three days after the thermic rise. The basal temperature was measured daily. In all the examined patients the combined treatment produced the appearance of the menstrual flow after the third therapeutical cycle. In 13 out of the 18 examined patients ovulation was observed. The hormonal dosage highlighted a clear increase in Gonadotropins and Estradiol levels.

Adolescent

[Treatment of hypothalamically-induced primary amenorrhea with epimestrol].

Eleven patients with hypothalamic primary amenorrhoea, aged between 17 and 23 years, were examined. Each patient was given 10 mg epimestrol (E) orally over a period of 10 days followed by a 20-day pause. This regimen was repeated 6 times. Gonadotropin secretory patterns were investigated between 9 a.m. and 2 p.m. before, during (on the 5th day of treatment in the 4th cycle) and 3 weeks after termination of treatment. In addition LHRH double stimulation tests were carried out before and after treatment to evaluate the acute releasable pool of gonadotropins as well as the pituitary synthesis capacity. In 3 patients with low baseline gonadotropin levels no effect of E on the release of gonadotropins could be found. These patients also showed non-pulsatile secretion with low baseline gonadotropin levels and no response in the LHRH stimulation tests. Similar results could be observed in one patient with low baseline LH levels but FSH levels within the normal range. Variable results were found in 7 patients with both LH and FSH in the normal range: 3 women experienced menstrual bleeding during and/or after E treatment; 1 woman stated that spotting had occurred twice. These 4 patients all showed regular pulsatile LH secretion after cessation of E treatment; the duration of the LH pulses was 60 to 120 minutes. Some hypothalamic activity seems to be essential for a positive response to E in patients with primary amenorrhoea. This activity is characterized by a positive gestagen test as well as baseline gonadotropin levels in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Induction of ovulation with Epimestrol (author's transl)].

Epimestrol 5 mg. daily for 10 days was administered in 119 treatment cycles to 21 women with normal gonadotropins and 33 ovulations were induced. Of the 21 patients, 7 had secondary amenorrhea, 10 had anovulatory oligomenorrhea and 4 had ovulatory oligomenorrhea. 17 patients desired pregnancies and 6 became pregnant. There was 1 pregnancy among 5 women with secondary amenorrhea. There were 3 pregnancies among 9 patients with anovulatory oligomenorrhea and 2 pregnancies in 3 patients with ovulatory oligomenorrhea. The pregnancy rate was 35%. Side effects were not observed.

Adult

Treatment of chronic anovulation and corpus luteum deficiency with epimestrol.

Ten patients presenting with anovulatory syndrome (AS, 4 patients), inadequate luteal phase (ILP, 3 patients) and short luteal phase (SLP, 3 patients) were treated with epimestrol for 29 cycles in total. The initial treatment was always 10 mg/day for 10 days followed by a modification of the daily dose and/or length of treatment needed. Ovulation was induced in all 4 AS patients with an adequate luteal phase (ALP) in 3 of them. In all other patients (with ILP and SLP) an ALP was induced; 2 of them became pregnant. No side-effects were reported.

Administration, Oral