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Clomiphene citrate: nuances of clinical application.

The results of administration of clomiphene citrate to 507 patients in 578 pregnancy attempts were evaluated with respect to pregnancy rate, outcome, sex ratio, and life table analysis. The effect of dose and concomitant administration of human chorionic gonadotrophin (hCG) was also assessed. The overall pregnancy rate was 38% by individual patient and 43% by patient attempt. A pregnancy rate of 61% was recorded for couples in which anovulation was the only reproductive problem. The abortion rate was 23% in a population screened by serum beta subunit hCG determination within a week of the missed expected menses. Many patients had multiple adverse fertility factors and fully 29% had been treated unsuccessfully with clomiphene citrate prior to entry into the program. The discussion includes results from the literature over the past two decades.

Abortion, Spontaneous↗

[A comparative study of monitoring induction of ovulation using clomiphene and HMG-HCG. Hormonal and ultrasound profiles (author's transl)].

The authors have studied daily hormone monitoring (Estradiol 17B, FSH, LH, Progesterone) and ultrasound (the size of the follicles and the number of the follicles) in 17 inductions using Clomiphene and 16 using HMG and HCG in cases mainly of dysovulation, but also of anovulation, in women who had previously been treated by induction that had failed. They establish the difference in the results obtained as far as (Estradiol 17B concerned, as far as the number of follicle that were stimulated or the size of the pre-ovulatory follicle, according to whether Clomiphene or sequential HMG-HCG had been used as a method of induction. They analyse the liability of the criteria for screening by plasma levels and by ultrasound and the correlation between these two parameters.

Adult↗

[Use of clomiphene for treating lactorrhea and amenorrhea].

The results are presented of clomiphene treatment of 22 patients with functional lactorrhea-amenorrhea. Lower therapeutic effect of this drug in comparison with that of parlodel was demonstrated in hyperprolactinemia. Combined clomiphene-parlodel treatment of lactorrhea-amenorrhea was studied in 12 patients, including 4 subjects with hypophyseal adenomas. It was shown that the combined use of these drugs enhances therapeutic activity without potentiating side effects.

Adult↗

Clomiphene citrate therapy of infertile women with low luteal phase progesterone levels.

Sixty-nine infertile women with a midluteal serum progesterone level of 4 to 14 ng/ml were treated with a graduated dosage schedule of clomiphene citrate until the progesterone level on day 21 was greater than 20 ng/ml. Thirty-one pregnancies occurred, 58% during the first adequate treatment cycle and 19% during the second cycle. The abortion rate was 23%. After 6 adequate treatment cycles, laparoscopic evaluation was performed on 28 of 39 patients who did not conceive. Pathology was noted in 57%. Seven of 17 patients with intraperitoneal causes of infertility conceived after alternative therapy. The corrected pregnancy rate was 60%. Results of this study suggest that low luteal phase progesterone levels may compromise fertility and that clomiphene citrate enhances pregnancy rates.

Adult↗

[Use of clomiphene in congenital adrenal cortical dysfunction].

The study of the functional state of the hypothalami-hypophyseal-ovarian system, using dexamethazone and clomiphene tests, has shown its ability to release gonadotropic hormones in response to stimulation and maintained relationship between the hypothalamus, hypophysis and ovaries in patients with congenital adrenocortical dysfunction. Further clomiphene administration was effective in patients, who suffered from congenital adrenocortical dysfunction with disturbed ovarian function, in spite of glucocorticoid treatment.

Adolescent↗

Steroid levels in the serum and seminal plasma during clomiphene therapy in hypofertile men.

The serum and seminal plasma concentrations of androstenedione, testosterone, dihydrotestosterone and 17beta-oestradiol were investigated in hypo- and oligospermic males during clomiphene-citrate, administration. A significant increase was demonstrated in the serum testosterone, dihydrosterone and 17beta-oestradiol values, mainly in the first month of therapy. The steroid increase in the ejaculate was less pronounced. Measuring of 17beta-oestradiol in serum appears to be a useful parameter for estimating the stimulative effect of clomiphene citrate.

Androgens↗

[Treatment of male infertility with clomiphene citrate (author's transl)].

Ninety unselected male patients with infertility were treated with clomiphene citrate, 25 mg/day, taken on 20 consecutive days each month for a period of 3 to 12 months. The patients were divided into two groups according to sperm counts. In 39 cases of oligozoospermia with sperm counts above 10 million/ml, six pregnancies were obtained (15.4%) while a significant improvement of sperm counts occurred in 22 cases (56.4%). On the other hand, in 51 cases with azoospermia or oligozoospermia below 10 million/ml only three pregnancies occurred (5.9%) and two patients (3.9%) had significantly improved sperm counts. The indications and form of administration of clomiphene citrate are commented upon.

Clomiphene↗

The effect of clomiphene treatment on different sperm parameters in men with idiopathic oligozoospermia.

76 men with idiopathic oligozoospermia mostly in addition to terato-asthenozoospermia, whose FSH level was in the middle or below the middle of the normal range, were treated with 50 mg clomiphene citrate daily for three months. Both mean sperm count per ml and total sperm count increased highly significantly (p smaller than 0.001). The changes in other physical sperm parameters were small and not significant(p greater than 0.05) except for the mean amount of motile spermatozoa and abnormal midpieces (excluding cytoplasmic droplets) and the mean quality of motility and sperm aggregation, which increased slightly but significantly (p greater than 0.05). The results of this study suggest that the beneficial effect of clomiphene citrate on sperm output in selected oligozoospermic men is not to a great extent at the expense of other physical sperm parameters.

Cell Aggregation↗

The effect of L-dopa and clomiphene citrate on peripheral plasma levels of luteinizing hormone-releasing factor.

Response of luteinizing hormone-releasing factor (LRF) and gonadotropin levels to orally administered L-dopa and clomiphene citrate were measured in 13 healthy female volunteers. Testing was carried out during the early follicular phase of the menstrual cycle. The results indicated a suggestive but statistically nonsignificant elevation of peripheral plasma LRF following L-dopa administration but no response following clomiphene ingestion. No acute increase in gonadotropin levels was demonstrated in either group. A low but statistically significant positive correlation was found between luteinizing hormone and LRF values determined from the same samples.

Administration, Oral↗

Update on the safety and efficacy of clomiphene citrate as a therapeutic agent.

Fifteen years have passed since our group first proposed the use of clomiphene citrate as an ovulation-inducing agent. Our 15-year experience with over 2,000 patients has not dampened our enthusiasm for this drug. The benefits have far outweighted the minor side effects or the possibility of multiple births. Serious birth defects were minimal and have been no greater than what one may expect in the general population. Clomiphene citrate has been a boon to womankind and deserves the confidence of both patient and physician: it is a drug with a record of utility and with but minor risks.

Abnormalities, Drug-Induced↗

[Dynamic tests with GN-RH L-dopa, clomiphene, HCG and HMG in normal adult men].

The plasma levels of gonadotrophins, androgens (expressed as testosterone) and 17beta-oestradiol in response to GnRH, L-dopa, clomiphene, HCG and HMG administration have been assayed by radioimmunological mehtods in 70 normal adult males. In keeping wih findings reported in the literature, the results obtained confirm the usefulness of dynamic stimulation with GnRH, clomiphene, and HCG in andrology for the purpose of evaluating the efficiency and integrity of the hypothalamic-pituitary-testicular system and of its individual glandular components. On the other hand, the administration of L-dopa and HMG does not appear to yield clinically useful findings.

Adult↗

Tamoxifen: an alternative approach in clomiphene resistant polycystic ovarian syndrome patients.

Twenty patients with ultrasound diagnosed polycystic ovaries and high luteinizing hormone levels who failed to respond to clomiphene citrate were given tamoxifen to induce ovulation. Tamoxifen 20 mg daily (group 1, n = 10) and 40 mg daily (group 2, n = 10) was given for 5 consecutive days from the third to seventh day of the cycle. Treatment was monitored by serial ultrasound scans and assessment of serum estradiol. Human chorionic gonadotrophin (hCG) was administered when at least one follicle was > 16mm and serum estradiol level was > 300 pg/ml per follicle. Ovulation was confirmed with detection of the follicular rupture ultrasonographically 2 days after hCG and midluteal progesterone levels. The ovulation rate achieved in group 2 patients was significantly higher (p = 0.01) than group 1. Three pregnancies were achieved in group 2 patients while there was no pregnancy in group 1. The only side effect was ovarian cyst formation in one patient in group 1. As a result, tamoxifen might be a good choice for clomiphene resistant patients prior to treatment with surgery or hMG.

Clomiphene↗

Massive ovarian edema in a woman receiving clomiphene citrate. A case report.

There have been 65 previously reported cases of massive ovarian edema. We present a case in a woman receiving clomiphene citrate. It is an uncommon, benign condition and usually involves the right ovary. Patients frequently present with intermittent abdominal pain, menstrual irregularities and occasional virilization. Incomplete ovarian torsion and edema formation secondary to a preexisting ovarian lesion are the postulated mechanisms. Our report is unusual because it is the first of massive ovarian edema in a woman receiving clomiphene citrate.

Adult↗

Hypothalamic-pituitary-ovarian response to clomiphene citrate in women with polycystic ovary syndrome.

OBJECTIVE: To examine the hypothalamic-pituitary sites of clomiphene citrate (CC) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Prospective controlled trial. PATIENTS, PARTICIPANTS: Seventeen women with PCOS and 9 normal-cycling women. INTERVENTIONS: Subjects with PCOS received CC, 150 mg/d for 5 days. MAIN OUTCOME MEASURES: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and LH pulse characteristics and their response to gonadotropin-releasing hormone (GnRH, 10 micrograms) were examined before and after 3 days of CC in PCOS subjects during a 12-hour frequent sampling study (n = 8). Daily urinary estrone glucuronide and pregnanediol glucuronide levels after CC were compared with concentrations in normal-cycling women through one menstrual cycle. In another nine PCOS subjects, pituitary and ovarian hormonal cyclicity was monitored by daily blood sampling. RESULTS: Thirteen of 17 treated cycles were ovulatory with normal luteal phases. In the ovulatory cycles, serum LH, FSH, estradiol (E2), and estrone levels increased after CC. Luteinizing hormone pulse frequency was unchanged, but LH pulse amplitude increased significantly after CC. Both LH and FSH response to exogenous GnRH was significantly attenuated after CC treatment. In anovulatory cycles, serum LH, FSH, and E2 increased initially and then returned to baseline and remained unchanged for the ensuring 40 days. CONCLUSIONS: Clomiphene citrate-induced ovulation in women with PCOS is accompanied by increased secretion of LH and FSH with enhanced estrogen secretion. The increased LH pulse amplitude after CC, together with decreased pituitary sensitivity to GnRH, suggests a hypothalamic effect.

Adolescent↗

Nonbacterial pyospermia: a consequence of clomiphene citrate therapy.

OBJECTIVE: Since the development of nonbacterial pyospermia in previously nonpyospermic men treated with clomiphene citrate (CC) has been observed, and nonbacterial prostatitis has been after antiestrogen treatment in an animal model, we sought characterize the occurrence of nonbacterial pyospermia in men treated with CC. PATIENTS AND METHODS: Forty-two nonpyospermic men with low serum testosterone levels treated with 25 mg CC/day were retrospectively compared to 27 untreated nonpyospermic men referred for infertility evaluation. RESULTS: Spontaneous nonbacterial pyospermia developed in CC-treated men [14.3%] at rate nearly twice that observed in controls [7.4%]. Serum testosterone increased in CC-treated men, both pyospermic and nonpyospermic. However, only CC-treated, nonpyospermic men demonstrated improvement in semen characteristics. CC-treated men who developed pyospermia were older than nonpyospermic men [pyospermic, 41.7 +/- 8.1 years; nonpyospermic, 35.6 +/- 4.9 years-P < .01). Men over 35 years of age were over six times as likely to develop pyospermia as men under 35 years of age (P < .05). Eight nonpyospermic, CC-treated men (8/36, 22.2%) have contributed to pregnancies leading to live births, whereas no pyospermic man has done so. CONCLUSION: These findings support an association between a nonbacterial inflammatory response of the human male reproductive tract and CC treatment. This pyospermia may occur without significant deterioration of semen characteristics and with an appropriate response to treatment in terms of serum testosterone level. Men over the age of 35 are statistically more likely to develop pyospermia with this therapy. Our results suggest that clomiphene citrate-associated pyospermia has a negative effect on male fertility.

Adult↗

Induction of ovulation with clomiphene citrate.

There are specific indications for the use of clomiphene. When used with the simple precautions that have been outlined, it is a safe, relatively inexpensive and convenient method of ovulation induction. Clomiphene certainly deserves its prominent place in the treatment of the infertile woman.

Amenorrhea↗

Effect of sexual steroid hormones and of clomiphene on the behavioral response to L-dopa in mice.

The scope of the present work was to ascertain the effects of some steroid hormones on the behavioral response of mice to L-Dopa. The drugs considered were: testosterone, mesterolone, cyproterone, estradiol, progesterone and clomiphene. The male sex steroids, having either androgen or antiandrogen properties, were able to potentiate the behavioral effect of L-Dopa in mice, while female sex steroids failed to demonstrate this activity. Clomiphene proved to be the most active in enhancing the behavioral effects of L-Dopa in mice.

Animals↗

The number of follicles and ovarian volume in the assessment of the response to clomiphene citrate in polycystic ovarian syndrome.

OBJECTIVE: To evaluate whether the number of follicles and ovarian volume have any significance in evaluating the response to clomiphene citrate treatment in Polycystic ovarian syndrome (PCOS). DESIGN: A prospective study of 70 infertile women, 44 of which were diagnosed with PCOS. SETTING: Zeynep Kamil Women and Children's Hospital Infertility Polyclinic. MAIN OUTCOME MEASURES: Follicle numbers and volumes in both ovaries, hormonal profile, response to Clomiphene Citrate (CC). Ovarian volume was significantly greater in PCOS cases than controls. However ovarian volume in the CC nonresponders was significantly greater than in CC responders in the PCOS group. The number of small follicles was significantly higher in PCOS cases than controls, and in the CC nonresponder group this number was also significantly higher than in CC responders. Endocrine features of patients with PCOS revealed that FSH, LH/FSH, DHEAS and Androstenedion do not discriminate between patients who respond to CC and those who do not respond. However, Testosterone (T) and LH levels differ significantly in responders and nonresponders. Small multiple follicles (> 9) and enlarged ovarian volume (> 6.8 ml) were the most prominent transvaginal ultrasonographic features of ovaries in CC nonresponsive patients with PCOS. Higher levels of T, LH, and significantly higher number of small follicles were associated with lack of CC response. These ultrasonographic features and laboratory assays could be clinically useful for distinguishing better the CC nonresponders from responders.

Adult↗