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PubMed1977

Clomiphene citrate therapy in a patient with Laennec's cirrhosis.

Clomiphene citrate therapy was initiated in a male with Laennec's cirrhosis complicated by gynecomastia, testicular atrophy, impotence, and loss of libido. The patient had abstained from alcohol and had stable hepatic function tests for 1 year before starting therapy. Luteinizing hormone and endogenous testosterone levels were maximally elevated with low dose therapy (50 mg per day). Follicle-stimulating hormone was maximally elevated with a dose of 100 mg per day and the elevation of total estrogen levels was not affected by increasing the dose. During treatment increase in testicular size was noted with resolution of impotence and improvement of libido which continued for 6 months after cessation of therapy. Gynecomastia remained unchanged despite the increased serum testosterone. Serum prolactin was normal before and after the clomiphene citrate. Semen initially unobtainable was analyzed after completion of therapy. The patient relapsed 8 months after the course of clomiphene citrate therapy.

Adult↗
PubMed1977

[Increasing the effectiveness degree of ovulation induction using clomiphene in combination with HCG in cases of functional sterility].

The authors gave functionally infertile women a combined treatment, of Clomiphen + HCG whom 19 had already been treated with Clomiphenor Epimestrol without success. If the number of ovulations considerably increase in consequence of Clomiphen + HCG treatment or the periods of ovulations, aphysiological periods, are of physiological duration the treatment may be successful. In these cases the effectiveness of Clomiphene induction can be intensified with HCG administration

Adult↗
PubMed1982

Menorrhagia associated with the wearing of IUD--the results of treatment with clomiphene citrate.

The influence of clomiphene citrate was tested in 206 women suffering from menorrhagia following the insertion of an intrauterine device (IUD). Eighty-three percent felt relief during the therapy, 10% did not benefit and 7% complained of a worsening of their symptoms. Among the women who felt an improvement, 85% responded to the 250 mg/cycle dosage, and 15% required the 350 mg/cycle dosage. Women with shortened menstrual cycles required the higher dose treatment, i.e. 350 mg, compared with women with normal cycles (36% vs. 28%, respectively). The influence of placebo was 6%. The hypothesis is raised that the mechanism of action of clomiphene citrate is the correction of the hormonal disturbances in the luteal phase of the cycle following insertion of the IUD.

Clomiphene↗
PubMed1986

Analysis of clomiphene isomers in human plasma and detection of metabolites using reversed-phase chromatography and fluorescence detection.

A method is described for the quantitative clinical analysis of plasma concentrations of the E and Z isomers of clomiphene, which is used in the induction of ovulation. The isomers of clomiphene, in addition to metabolites, are extracted from plasma with tert-butyl methyl ether (MTB). The MTB layer is dried, reconstituted and an aliquot subjected to chromatography. The drug and metabolites are separated by reversed-phase high-performance liquid chromatography. The eluent is fed into a knitted or braided, cylindrical reaction coil made of Teflon, into which is inserted a low-energy mercury lamp. This results in a photoinduced stilbene-to-phenanthrene oxidation yielding highly fluorescent analytes; this provides excellent sensitivity for the quantitation of the intact drug isomers and the detection of presently uncharacterized metabolites. Use of the reversed-phase chromatographic mode results in elution of the polar metabolites prior to the intact drug isomers. A combination of reversed-phase chromatography and an in-line post-column reaction coil results in a sensitive method that is more reliable and rapid than those previously reported and is applicable to the routine analysis of clinical samples. The method has been applied to individual isomers of clomiphene in plasma at concentrations of 0.06-600 ng/ml.

Journal Article↗
PubMed2001

Treatment of chronic anovulation resistant to clomiphene citrate (CC) by using gonadotrophin-releasing hormone agonist (GnRH-a) ovarian suppression followed by recombinant follicle-stimulating hormone (r-hFSH) treatment (Suprecur, Puregon).

We performed a prospective study to assess the effects of a starting dose of 50 units of recombinant follicle stimulating hormone (Puregon) during gonadotrophin-releasing hormone agonist therapy (Suprecur) on follicular development in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). In a prospective clinical trial, 25 women with clomiphene citrate-resistant PCOS who wanted to become pregnant were treated by a low-dose step-up protocol of SC recombinant follicle stimulating hormone administration during gonadotrophin-releasing hormone agonist therapy, monitored by transvaginal ultrasonography and retrospectively by serum endocrine assays taken at each monitoring visit. Cancellation of cycles, ovulation, rate and size of follicles growth, serum E2 concentration and pregnancy were recorded. All patients exhibited a response: 22 patients ovulated, of whom 10 conceived. Using the low-dose protocol during gonadotrophin-releasing hormone agonist therapy permitted induction of ovulation safely and successfully in patients with clomiphene citrate-resistant PCOS who were patients previously difficult to treat with the conventional ovulation induction protocol.

Journal Article↗
PubMed1983

Clomiphene citrate therapy for luteal phase defect.

The incidence of luteal phase defects in 366 infertility patients was 12.7%. Life-table analysis was used for determination of the conception rate with clomiphene citrate therapy, and with this method, evidence was found for the presence of two subgroups with respect to response. The crude conception rate was 40.9%. In a group of patients with a luteal phase defect and no other infertility factors, those that conceived had a significantly larger mean biopsy delay than those who did not (6.28 days versus 4.32; P less than 0.02). In a group with a histologic delay of 5 days or more, the conception rate was 79%, while the rate was only 8.9% in those with a less severe deficit (P less than 0.001). Theoretic considerations for clomiphene citrate therapy are discussed.

Actuarial Analysis↗
PubMed1983

Clomiphene in the treatment of adolescent gynecomastia. Clinical and endocrine studies.

Twelve boys, aged 12 to 19 years, with persistent gynecomastia were treated with the antiestrogen, clomiphene citrate, at a dose of 50 mg/day by mouth for one to three months. The mean breast size decreased by 0% to 36%, with only five boys experiencing a reduction of greater than 20%. Five boys subsequently required reduction mammoplasty. Levels of urinary gonadotropins, serum testosterone, and estradiol increased significantly during therapy. Since the ratio of testosterone to estradiol remained unchanged during treatment, the antiestrogen effects were achieved primarily at the level of breast tissue. Clomiphene citrate in a dose of 50 mg/day resulted in only small decreases in persistent pubertal gynecomastia and was not a satisfactory medical therapy for the condition.

Adolescent↗
PubMed2000

Clomiphene or tamoxifen for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. The administration of anti-oestrogens is a common treatment because anti oestrogens interfere with the normal negative feedback of sex steroids at hypothalamic and pituitary levels in order to increase endogenous gonadotropin-releasing hormone secretion from the hypothalamus and FSH and LH secretion directly from the pituitary. In turn, FSH and LH stimulate Leydig cells in the testes, and this has been claimed to lead to increased local testosterone production, thereby boosting spermatogenesis with a possible improvement in fertility. There may also be a direct effect of anti-oestrogens on testicular spermatogenesis or steroidogenesis. This review considers the available evidence of the effect of both Clomiphene citrate and tamoxifen, both of which have a predominant anti-oestrogenic effect, for idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective was to assess the effects of treating subfertile men with anti-oestrogens (clomiphene or tamoxifen) on pregnancy rates among couples where subfertility has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of anti-oestrogen therapy for 3 months or more compared to placebo or no placebo for subfertile males among couples where subfertility is attributed to male factor. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Any differences were resolved with a third reviewer. MAIN RESULTS: Ten studies involving 738 men were included. Five of the trials did not specify method of randomisation. Anti-oestrogens had a positive effect on endocrinal outcomes, such as serum testosterone levels. In trials with secure randomisation there was no difference in the pregnancy rate between the anti-oestrogen groups and the control groups (odds ratio 1.26, 95% confidence interval 0.99 to 1.56). The overall pregnancy rate for these five trials was 15.4% compared to the spontaneous rate of 12.5% in the control groups. These odds increased to 1.56 (95% confidence interval 0.99 to 2.19) when all 10 trials were included, but this result is likely to be artificially inflated. REVIEWER'S CONCLUSIONS: Anti-oestrogens appear to have a beneficial effect on endocrinal outcomes, but there is not enough evidence to evaluate the use of anti-oestrogens for increasing the fertility of males with idiopathic oligo-asthenospermia.

Clomiphene↗
PubMed1994

Transabdominal ultrasonographic evaluation of endometrial thickness in clomiphene citrate-stimulated cycles in relation to conception.

The possible antiestrogenic effect of clomiphene citrate on endometrial growth was assessed by serial transabdominal ultrasonographic measurements in 46 women with unexplained infertility. A significantly higher (p < 0.05) rate of endometrial growth was observed in the 8 women who conceived compared with the 38 women who failed to conceive. A thicker endometrium (4.6 +/- 0.3 mm) was observed from the third day before ovulation as well as a higher average growth rate in the three days prior to ovulation (0.7 +/- 0.1 mm/day) in the group that achieved pregnancy compared to a lower endometrium (2.1 +/- 0.2 mm) from the third day before ovulation and a slower growth rate in the three days prior to ovulation (0.2 +/- 0.0 mm/day) in the group that did not achieve pregnancy (p < 0.05). These data suggest that clomiphene citrate may exert an antiestrogenic effect on the endometrium, and thus interfere with implantation.

Adult↗
PubMed2001

Oral administration of clomiphene to neonatal rats causes reproductive tract abnormalities.

Oral administration of clomiphene at 2, 4, or 8 mg/kg to 4-day-old rats caused multiple histopathological abnormalities of the reproductive tract in both male and female animals. No histopathological abnormalities were observed in 30-day-old male rats at any dose examined. In contrast, 30-day-old females showed hypertrophy of the myometrium at all doses examined, and hypertrophy of the luminal or glandular epithelium, and dilatation of the uterine lumen were observed in the highest dose group. In post-pubertal rats, histopathologically marked changes were observed in the testes and epididymides in males, and in the ovaries and uterus in females in the highest dose group. In addition, relative weight of male reproductive organs in the highest dose group was decreased as compared with that in the controls. These results suggested that early neonatal exposure to clomiphene induced marked reproductive tract abnormalities in males after puberty, as well as in females.

Abnormalities, Drug-Induced↗
PubMed1987

Laparoscopic ovarian electrocautery in patients with polycystic ovarian disease resistant to clomiphene citrate.

Eleven patients with polycystic ovarian disease resistant to clomiphene citrate were treated by ovarian electrocautery. Nine patients ovulated after electrocautery, and five became pregnant (four-following additional treatment with clomiphene citrate). Testosterone and androstenedione levels were reduced, but androstenedione levels returned to pretreatment values at 6 months.

Adult↗
PubMed1985

Preliminary experience with a combination of clomiphene and variable dosages of menopausal gonadotropins for enhanced follicular recruitment.

A combination of clomiphene citrate and human menopausal gonadotropin was employed for enhanced follicular recruitment in an in vitro fertilization program. All patients received 50 mg of clomiphene and 1 ampule of human menopausal gonadotropin daily from cycle day 5 through cycle day 9. Follicular monitoring was begun on day 10 using a combination of ultrasound measurement of follicular size and number and determination of peripheral estradiol levels. Based on the size and number of follicles, the peripheral levels of estradiol, and the rate of follicular growth and increase in estradiol, human menopausal gonadotropin was continued at a dosage of 1 to 3 ampules/day through the day of human chorionic gonadotropin administration. Human chorionic gonadotropin was administered on the evening of the day the largest follicle reached or exceeded 20 mm in mean diameter if the estradiol levels had been rapidly rising or reaching a plateau and had exceeded a minimal level of 300 pg/ml. Using this protocol, 30 of 33 patients underwent laparoscopy, 29 patients had successful oocyte recovery, and 23 patients underwent embryo replacement, with the establishment of six clinical pregnancies.

Clomiphene↗
PubMed1986

Oocyte maturation inhibitor activity in human follicular fluid: quantitative determination in unstimulated and clomiphene citrate- and human menopausal gonadotropin-stimulated ovarian cycles.

Since removal of the oocyte from the intrafollicular milieu allows meiotic resumption and germinal vesical breakdown to proceed, the concept of an intrafollicular oocyte maturation inhibitor (OMI) has evolved. Accordingly, we asked the following questions: Is there OMI activity in human follicular fluid? Does OMI activity change with ovarian hyperstimulation? and Does OMI activity correlate with oocyte fertilization or the concentration of steroids in the corresponding follicular fluid? Fresh cumulus enclosed porcine oocytes from small follicles were incubated with human follicular fluid aspirates from normally menstruating patients with or without treatment: unstimulated follicles (N = 10), clomiphene citrate (150 mg/day) (N = 10)-treated cycles, and human menopausal gonadotropin (hMG) (N = 12)-treated cycles. A lyophylized porcine follicular fluid standard and serum-free culture media were used as positive and negative controls, respectively. After a 40-hr incubation with test materials, the oocytes were fixed, stained, and evaluated for oocyte maturation as determined by germinal vesical breakdown. Human follicular fluid, estradiol, progesterone, androstenedione, and testosterone levels were determined by radioimmunoassay. The 50% inhibitory dose (ID50) for OMI activity in follicular fluid from untreated, spontaneously menstruating women was less than that for follicular fluid from clomiphene-stimulated patients, which was less than that for follicular fluid from hMG-stimulated patients. The difference between OMI values from untreated and hMG-stimulated follicular fluids was statistically significant. Human oocytes removed from follicular fluid with higher OMI activity tended not to fertilize in vitro compared to the relatively lower OMI activity present in follicular fluid yielding oocytes which did fertilize.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of clomiphene citrate and leuprolide acetate on luteal-phase hyperprolactinemia during ovarian stimulation with menopausal gonadotropins.

Hyperprolactinemia, a known modulator of reproductive function, occurs commonly in women undergoing ovarian stimulation with human menopausal gonadotropins (hMG). Clomiphene citrate (CC) and gonadotropin releasing hormone analogues (GnRHa), when administered during the luteal phase, attenuate the hyperprolactinemic response to hMG. We asked whether follicular-phase administration of CC and GnRHa, as employed clinically in women undergoing ovarian stimulation for in vitro fertilization or gamete intrafallopian transfer, would alter the incidence and severity of hMG-induced luteal-phase hyperprolactinemia. Seventy-five percent of all patients had at least one luteal prolactin level greater than 25 ng/ml, and 40% had mean luteal-phase prolactin levels greater than 25 ng/ml. The incidence of hyperprolactinemia was similar in pregnant and nonpregnant cycles. The incidence of hyperprolactinemia was similar for both the GnRH agonist-treated group and those given clomiphene citrate. The increase in mean luteal prolactin levels over the follicular-phase baseline level was significantly greater in the CC-treated group (P = 0.03). This was due to the significant suppression of follicular-phase baseline prolactin levels in patients receiving CC. We conclude that neither CC nor GnRHa administration in the follicular phase prevents luteal-phase hyperprolactinemia in women undergoing ovarian stimulation with hMG.

Clomiphene↗
PubMed1989

The effect of clomiphene citrate on human preovulatory oocyte maturation in vivo.

Sixty-four infertile women underwent diagnostic laparoscopy in the periovulatory period at time-bracketed intervals following their endogenous luteinizing hormone (LH) surge. Forty-eight of these women were studied during natural cycles and 16 had mild oligoovulation and were administered clomiphene citrate (CC) to regulate their cycles. No patient received human chorionic gonadotropin. No patient was undergoing either in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). Follicle puncture was performed and the oocytes were observed immediately for stage of maturation. Oocytes obtained from follicles exposed to CC were found to require an increased interval of time to reach metaphase I compared to oocytes obtained from natural cycles (27.75 +/- 2.2 vs 22.5 hr; mean +/- SE). Furthermore, the interval of time required for metaphase I oocytes to achieve metaphase II was statistically significantly shortened for CC cycles (2.4 hr for CC vs 10 hr for natural cycles. Nevertheless, there was no difference between natural and CC cycles in the time interval between LH surge onset and ovulation. These in vivo findings suggest a direct effect of CC on human oocyte maturation and may help explain the well-established discrepancy between the relatively high ovulation rate and the relatively low conception rate in clomiphene-induced cycles.

Clomiphene↗
PubMed1988

A short luteal phase in cycles stimulated with clomiphene and human menopausal gonadotropin for in vitro fertilization.

Of 70 cycles stimulated with clomiphene and human menopausal gonadotropin (hMG) for an in vitro fertilization-embryo transfer (IVF-ET) program, a short luteal phase of 11 days or less was found in 18. In this group the mean estradiol and progesterone levels were elevated in the early luteal phase. Despite the elevated initial values, progesterone levels fell rapidly at the mid luteal phase as a sign of premature luteolysis. The mean total amount of gonadotropin administered and the mean number of follicles punctured and of oocytes recovered did not show any significant difference between the groups of normal and short luteal phases. The present findings support the theory that hyperestrogenism in the early luteal phase may initiate the premature luteolysis observed in clomiphene-menopausal gonadotropin-stimulated cycles.

Clomiphene↗