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PubMed1988

[Clomiphene citrate therapy in idiopathic male infertility].

Clomiphene citrate therapy was performed on 30 patients with idiopathic male infertility, who were intractable to non-hormonal therapy. Clomiphene citrate was administered orally at a dose of 25 mg per day for 25 days with 5 days of rest following Paulson' protocol, and we favorable results were obtained: Both sperm count and sperm motility improved in 11 cases (36.7%). Odera's score count decreased in 14 cases (46.7%), which were judged as effective. The wives of 4 patients treated by this therapy became pregnant. After this therapy, the serum levels of luteinizing hormone, follicle stimulating hormone, testosterone and prolactin were 1.90, 1.81, 1.89 and 1.22 times higher, respectively. These findings indicate that clomiphene citrate therapy is an effective for idiopathic male infertility, but we need to consider that the sudden and marked elevation of serum testosterone level by this therapy might affect male accessory sex organs such as the prostatic gland which shows androgen dependency later in life.

Clomiphene↗
PubMed1977

[Dynamic tests with GnRH, L-dopa, clomiphene, cyclophenyl, HCG and HMG in 98 cases of dysspermia due to a variety of causes].

Radioimmunological methods have been used to assay the plasma concentrations of gonadotropins, androgens (expressed as the sum of testosterone and dihydrotestosterone) and 17beta-oestradiol in 98 patients suffering from dysspermia of variable etiology, after stimulation with GnRH, Clomiphene, L-Dopa, Cyclophenyl, HCG in various dosage schemes, and HMG. Results show L-Dopa and HMG tests to be of little value in assessing the endocrine function in infertile men. They also confirm, in keeping with data found in the literature the usefulness of dynamic stimulation with GnRH, Clomiphene, and HCG for purposes of andrologic diagnosis. The GnRH proved useful for the distinction between primary and secondary hypogonadotropism as well as for assessing the therapeutic efficacy of releasing factors. The functional efficacy of the endocrine axis which is often impaired in patients with dysspermia can be evaluated by the Clomiphene test. In the small number of cases in which it was applied, Cyclophenyl brought about changes in gonadotropin concentration which require further study. The HCG tests, to be performed in patients with lower than normal testosterone plasma lavels, permits the discrimination between primary and secondary Leydig cell deficiencies as well as the assessment of interstitial tissue sensitivity to chorionic gonadotropin stimulation. Of the three dosage schemes (5000 IU, 7500 IU "step up", 10.000 IU) the last one is most suitable for clinical use.

Adult↗
PubMed1977

[Effects of clomiphene and estrogens on circulating gonadotropins, testosterone, androstenedione, in old menopausal women (author's transl)].

The threshold of sensitivity of the gonadostat has been tested in 20 old menopausal women by clomiphene (50 or 200 mg/day for 5 days) and/or low doses of ethinyl oestradiol (EE2) (10 or 20 microgram/day). Clomiphene did not increase nor decreased serum levels of LH-FSH and testosterone (T) but increased significantly androstenedione (A) levels. Even at the lower dosage used, EE2 decreased drastically the levels of LH but less completely that of FSH. Clomiphene breaks off partially the oestrogen's blockade on FSH but not on LH. No modification was observed for T and A even after 30 days of estrogen therapy. This data shows the peculiar sensitivity of the gonadostat in advanced menopaused women. It also suggests that the gonadostat exhibits a low threshold of sensitivity analogous to that observed in late prepubertal period. Moreover, the different behaviour of LH and FSH in response to the negative feedback of oestrogens supports that an ovarian factor, distinct from estrogens and missing during menopause plays a role in the regulation of FSH.

Clomiphene↗
PubMed1986

[Parameters of ovulation in clomiphene citrate treated cycles. The effect of pre-ovulatory administration of oestrogen and human chorionic gonadotropin].

This study was undertaken to evaluate the parameters used for monitoring ovulation in patients on clomiphene citrate treatment for the induction of ovulation. The mean serum oestradiol level for every follicle larger than 17 mm on the day before ovulation was 1 885 pmol/l. This value is significantly higher than the value found in spontaneous cycles. The maximum average pre-ovulatory follicle size was 22 mm, also significantly larger than in spontaneous cycles. The maximum pre-ovulatory cervical mucus score is significantly lower than that found in spontaneous cycles. The average midluteal serum progesterone and oestradiol values were significantly higher than in spontaneous cycles. These differences should be taken into consideration in interpreting the results of patients treated with clomiphene citrate for ovulation abnormalities and before in vitro fertilization. Seven patients with a healthy cervix had poor cervical mucus scores in spite of high pre-ovulatory serum oestradiol levels; scores did not improve with administration of exogenous oestrogen, but became optimal with subsequent human menopausal gonadotrophin treatment. Poor cervical mucus despite ovulation and adequate pre-ovulatory serum oestradiol levels in patients on clomiphene treatment should therefore be considered as an indication for gonadotrophin treatment. Pre-ovulatory administration of human chorionic gonadotrophin had no effect in increasing midluteal serum progesterone and oestradiol levels.

Cervix Mucus↗
PubMed1979

Morphological findings in granular reticulum of arcuate nucleus neurons after clomiphene citrate administration.

The action of high doses of clomiphene citrate on the rough endoplasmic reticulum of the hypothalamic arcuate neurons of male cat has been studied. Clomiphene (250 mg/kg) produces an accumulation of typical paracrystalline material in the rough endoplasmic reticulum. After the administration of a protein-synthesis inhibitor no such material was observed in clomiphene-treated cats. The possibility exists that the specific ultrastructural changes seen indicate an increased protein synthesis in hypothalamic arcuate neurons.

Animals↗
PubMed1982

The preovulatory follicular fluid in the human: influence of hormonal pretreatment (clomiphene-hCG) on some biochemical and biophysical variables.

Some biochemical and biophysical variables of human follicular fluid have been studied both in normal women after the LH peak (preovulatory follicles) and in women treated with clomiphene and hCG (clomiphene treated follicles). The results showed that lactate and glucose levels are different from those found in serum but are not influenced by the clomiphene treatments. Osmolarity and enzymatic contents are neither different from those of serum nor modified by the hormonal treatments. The transfer of water across the follicle wall was found to be closely regulated because only slight variations were observed in the wide range of volumes collected in the samples examined.

Adult↗
PubMed1983

Luteal phase evaluation after clomiphene-chorionic gonadotrophin-induced ovulation.

Fifty infertile patients treated with clomiphene and hCG for induction of ovulation were studied with plasma progesterone measurement and endometrial histology. Five patients (10%) presented defective endometria and low plasma progesterone in spite of biphasic BBT charts with normal luteal phase length. Forty-five patients (90%) had significantly higher plasma progesterone concentrations than those found in a control group of fertile women, but a defective endometrial secretory pattern occurred in 19 of these 45 patients (42.3%). These data suggest the need for monitoring the response to clomiphene by endometrial histology in addition to BBT and plasma progesterone, or for supplemental therapy to overcome the endometrial luteal phase deficiency in clomiphene-treated cycles.

Adult↗
PubMed1983

[Treatment of corpus luteum insufficiency-induced functional sterility with clomiphene].

Two hundred and fifty-six women were treated with clomiphene citrate. As a consequence of treatment preovulatory FSH concentration of the serum increased. There was an improvement of the luteal function in 84.0% of the patients, and 53.9% of them became pregnant. Based on the above data the authors consider clomiphene citrate suitable for treatment of luteal dysfunction. In a number of cases clomiphene treatment proved to be effective even after failure of the gonadotropin treatment.

Adult↗
PubMed1984

Response of the cervical factor to combined treatment with clomiphene and ethinyl-oestradiol.

Combined clomiphene + ethinyl-oestradiol therapy was applied to 103 women with functional infertility. Ovulatory responses were obtained with clomiphene in a number of cases, but no pregnancy ensued. Ethinyl-oestradiol was then administered in low doses together with clomiphene over 3 cycles until the day before the expected date of ovulation. This resulted in a further increase in the number of ovulatory cycles, and one-third of the women had become pregnant. Comparing the two types of treatment on the basis of quality, quantity and sperm-penetration of the cervical mucus, low doses of oestradiol were found to affect these parameters favourably. If the treatment is unsuccessful, i.e. if the parameters of mucus or of the conditions of penetration fail to respond, further investigations are required to find out whether a permanent damage to the cervical epithelium or some penetration disorder of immunological origin is responsible for the infertility.

Adult↗
PubMedDate not supplied

Effect of clomiphene citrate on the testis, epididymis and accessory sex glands of the musk shrew (Suncus murinus L.).

The effects of oral administration of clomiphene citrate (50 mg/kg body weight) on the testis, epididymis and accessory sex glands of the musk shrew were investigated. The drug induced duration-dependent alterations in the weight and histology of these organs. The drug produced significant reduction in testicular weight with severe degenerative changes in seminiferous tubules; Leydig cells were also atrophied. However, no significant change was found in the levels of protein, RNA and DNA in the testes of drug-treated animals as compared with controls. Epididymis in drug-treated shrews exhibited significant decrease in weight and regressive histological changes. Spermatozoa collected from the cauda epididymidis of drug-treated shrews were immotile and often fragmented. Clomiphene treatment also induced regressive histological changes in the prostate and ampullary gland accompanied by significant decrease in the weight. The treatment also caused significant decrease in the level of fructose in the ampullary glands. Following withdrawal of the drug, the reproductive organs returned to their normal state. Full recovery was noticed in the accessory sex glands 28 days after drug withdrawal. However, full spermatogenic activity and normal epididymal histology were achieved only after 56 days The mechanism of action of clomiphene on the male reproductive organs is briefly discussed.

Animals↗
PubMed1984

[Ovulation induction with clomiphene and dexamethasone].

Combined clomiphene-dexamethasone-treatment was applied to 20 patients and 5 pregnancies were successfully induced. The women received 150-200 mg/die clomiphene from the fifth through the ninth days of their cycles, and 2 mg/die dexamethasone from the fifth to the fourteenth days of cycle. Three of the 5 pregnancies were closed successfully and two by caesarean section, one of them with twins. The combined clomiphene-dexamethasone-treatment is recommended as a sterility therapy.

Adult↗
PubMedDate not supplied

[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↗
PubMed1978

[Experiences with clomiphene therapy of endocrine sterility].

Two hundred seventy-three infertile women with disturbances of the menstrual cycle were treated with clomiphene citrate a level of 50 or 100 mg daily for 5 days, or even--in cases of therapeutic failure--of 150 or 200 mg daily. According to the experiences of other authors the results indicate that conception can be obtained in a rate between 35 and 40%. The frequent occurence of additional factors diminishing fertility, however, reduces this relatively favorable pregnancy rate to a level of 30% under the conditions of practice. Patients with ovulatory failures, secondary amenorrhoe associated with sufficient endogenic estrogen secretion, and luteal insufficiencies respond most favorably to clomiphene citrate. If the preovulatory cervical mucus reaction is missed, the additional application of an estrogen preparation, in cases of repeated luteal phase defects the combination of clomiphene with HCG is recommended.

Amenorrhea↗
PubMed1980

[Timing of ovulation in clomiphene-induced cycles (author's transl)].

214 menstrual cycles, induced by clomiphene in 121 women desiring a family but manifesting disturbances of cycle, type WHO II (1976) were investigated with regard to pattern of cervical function. 184 were ovulatory cycles. The time of ovulation was predictable within a range of two days in 58.7% of cases by means of the cervical score, consisting of the dilatation of the cervical os, the degree of transparency, the quantity and the consistency of the cervical mucus. The occurence of the "LH peak" and the rise in basal body temperature (BBT) were set in relation to this. In 41.3% of cycles the cervical score, influenced by the antioestrogenic effect of clomiphene, gave only insufficient evidence. In subsequent treatment cycles the cervical function, in relation to the individual case and the inducible quality of the cycle, showed a similar response rate as in the first treatment cycle. Our results suggest that, after examination of the first clomiphene-induced cycle by the combined means of cervical score and hormoneanalytic methods, patients with a positive cervical response, can be investigated by any interested doctor, even if he doesn't have a laboratory at his disposal, in order to assess the timing of ovulation for therapeutic measures.

Body Temperature↗
PubMed1982

[Therapeutic results obtained from women with functional sterility. Second communication: clomiphene therapy (author's transl)].

Reported in this paper are results obtained from treatment of 246 patients for sterility in WHO Group II to whom clomiphene had been applied. Some of these patients had been earlier treated without success, using combined oestrogen-gestagen preparations. Primary sterility was manifest in 86 per cent of the cases, and biphasic cycle was recorded from 95 per cent of the probands.--The pregnancy rate was 30.1 per cent, but 22 per cent of pregnancies ended in abortion. Multiple pregnancy was observed in four per cent. Minor side effects occurred in 1.2 per cent of the cases.--Best results were 36 per cent in cases of secondary amenorrhoea and 32 per cent in cases of anovulation. Sixty-six per cent of all pregnancies occurred in the first three cycles of treatment. Eight per cent of the women grew pregnant six months within discontinuation of clomiphene medication. An unambiguous interdependence was found to exist between age of the patient, length over time of desire of children, and rate of conception. The pregnancy rate fell to 15 per cent in women beyond 30 years of age. A pregnancy rate of 35 per cent was achieved in 110 women in whom sterility had been solely caused by functional aspects, while 27 per cent were achieved for couples with additional fertility-depressing factors. Moderate increase of clomiphene doses, homologous insemination, and flanking HCG injections helped to improve success of the basic therapy to the order of 119 per cent.--Efforts in terms of monitoring and general therapeutic input are higher than those associated with ovarian hormone therapy of sterile couples, though justified by better results.

Abortion, Habitual↗
PubMed1978

Continued clinical experience with an increasing dosage regimen of clomiphene citrate administration.

Between August 1, 1975, and July 31, 1977, 60 patients with infertility and ovulatory dysfunction were evaluated at the Naval Regional Medical Center, Oakland. Of these, 15 had incomplete work-ups or were lost to follow-up. Of the remaining 45 patients, 2 (4.5%) failed to ovulate at a maximal dose of 250 mg of clomiphene for 5 days with 10,000 units of human chorionic gonadotropin. Of the 43 (95.5%) who did ovulate, 33 conceived. Of these 33 patients, 9 (27%) required greater than 100 mg of clomiphene and/or longer than three ovulatory cycles to conceive. Of the 10 patients who did not become pregnant, additional infertility factors were present in 5. When these 5 were eliminated, the corrected pregnancy rate was 87% (33 of 38). The spontaneous abortion rate was 12.2% and there were no multiple gestations. These results would further emphasize that clomiphene can be used safely and effectively at doses greater than 100 mg or for longer than three ovulatory cycles.

Anovulation↗
PubMed1978

Ovarian and hypothalamic response to sequential increases in the amount of clomiphene administered to the same group of oligomenorrhoeic women.

Ten patients with oligomenorrhoea were investigated using increasing doses of clomiphene citrate in each cycle. The starting dose was 50 mg on day 1 of the cycle for 5 days and was increased by 50 mg per day for 5 days per cycle, to a maximum dose of 200 mg per day. Urinary total oestrogen concentration was measured on Day 1 to 3, 12 to 14 and on Day 21. Peripheral venous plasma concentrations of immunoreactive LH & FSH on Days 1 to 3 and 12 to 14 and the peripheral venous plasma concentration of immunoreactive progesterone on Day 21 were measured. The response to treatment is discussed in relation to hormone levels in the early follicular phase and to the dose of clomiphene administered. No correlation was found between hormone levels in the early follicular phase and increments in oestrogen and LH concentrations at midcycle. On a low dose regime the increment in FSH at midcycle was significantly greater in patients with a normal FSH concentration in the early follicular phase than in those with a low FSH level at this phase in the cycle. The results of treatment with clomiphene were not changed by an increase in dose from 50 mg to 150 mg but an increase to 200 mg significantly reduced the magnitude of response.

Adult↗
PubMed1976

A reduction in multiple pregnancies following the use of a clomiphene citrate: human gonadotrophin sequence.

The results of stimulation with gonadotrophins at the Sterility Clinic (Crown Street) are presented. Two different techniques have been employed involving 86 patients. All patients have similar indications for treatment. All have received the same preliminary investigations and all have been treated previously with a minimum of three cycles of Clomiphene Citrate without satisfactory response (i.e. "clomid failures). Technique (1) involved 51 patients and consisted of daily injections of Human Pituitary Gonadotrophin (H.P.G.) followed by an ovulating injection of Human Chorionic Gonadotrophin (H.C.G.) and a follow up injection of H.C.G. on post-ovulatory Day 7 or 8. This technique had a pregnancy rate of 64 per cent and a multiple pregnancy rate of 34 per cent. Technique (2) involved 35 patients and consisted of 5 days priming with Ethinyl Oestradiol and Clomiphene Citrate together, followed immediately by daily injections of H.P.G., then an ovulating injection of H.C.G. and a follow up injection of H.C.G. on post-ovulatory Day 7 or 8. The results of this variation in technique were a pregnancy rate of 69 percent, a multiple pregnancy rate of 8 percent. It is suggested that the use of Clomiphene Citrate in the latter technique acts as a "buffer" against the more extreme ovarian responses to H.P.G. acting alone and has the apparent advantage of a higher pregnancy rate, a lower multiple pregnancy rate and a reduction in the number of foetuses in each of the multiple pregnancies.

Chorionic Gonadotropin↗