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PubMed1977

Effects of clomiphene citrate administraiton on the hypothalamo-pituitary-gonadal axis of male chronic schizophrenics.

The clomiphene citrate stimulation test was performed in 16 adult male chronic hebephrenic schizophrenics (10 off therapy from 3 months to 1 year and six on therapy with phenothiazines or haloperidol) and in five normal controls, matched for age. Clomiphene citrate was given orally at a daily dose of 150 mg, divided into three doses, for 8 days. FSH, LH and testosterone levels were assayed before the administration of clomiphene citrate and after 4 and 8 days of treatment. Schizophrenics showed normal increase of FSH levels during the clomiphene administration, while LH and testosterone responses were blunted. Phenothiazines or haloperiodol had no effect on the test.

Adult↗
PubMed1971

Amenorrhoea in anorexia nervosa: assessment and treatment with clomiphene citrate.

Seven patients with anorexia nervosa were studied, three during the acute stages of the illness, and four in whom weight gain had been achieved, but who suffered from persistent amenorrhoea of 18 to 79 months' duration.In the acute stage all patients had low serum luteinizing hormone (LH) levels which were unresponsive to clomiphene citrate. In those who had regained weight the mean basal LH levels were normal, and they responded to clomiphene with an initial doubling of serum LH during administration of the drug, followed by a second peak of serum LH four to seven days after the drug was stopped. Menstruation occurred in these patients 13 to 19 days after the clomiphene was discontinued, and in two patients regular spontaneous menstruation was initiated.The low LH levels unresponsive to clomiphene in the acute stage provide evidence for a hypothalamic abnormality in anorexia nervosa. After regain of body weight the drug seems to be effective in treating the amenorrhoea which may be persistent.

Acute Disease↗
PubMed1989

Ovulation following combined therapy with wen-jing-tang and clomiphene citrate therapy in anovulatory women.

The effect of combined therapy with Wen-Jing-Tang and clomiphene citrate on anovulation was studied in 16 infertile patients who did not respond to clomiphene citrate alone. Wen-Jing-Tang was given at a dose of 5 g a day every day from day 2 of the menstrual cycles and clomiphene citrate was given at 150 mg a day for 5 days from day 5 of the cycle. Ovulation occurred in 43.8% of the patients and 48.6% of the cycles. No case of ovarian hyperstimulation syndrome or pregnancy were observed. These results suggest that the combined therapy with Wen-Jing-Tang and clomiphene citrate should be used before therapy with human menopausal gonadotropin.

Adult↗
PubMed1996

Induction of ovulation with the sole use of clomiphene citrate in late-onset 21-hydroxylase deficiency.

Late-onset 21-hydroxylase deficiency (21-OHD) is a congenital enzymatic defect in the glucocorticoid and mineralocorticoid steroidogenic pathways. The manifestations, including hirsutism and infertility, usually occur at puberty or young adulthood. In infertile, anovulatory women with late-onset 21-OHD, the usual therapy is glucocorticoids for ovulation induction. In this case, we report the sole use of clomiphene citrate to induce ovulation in a patient with late-onset 21-OHD. A hirsute and oligomenorrheic woman was diagnosed as having polycystic ovary syndrome at age 25. Her hirsutism responded to oral contraceptives. At age 31, she was given clomiphene citrate alone for ovulation induction and conceived in her fourth cycle. At age 36, because of increased hirsutism she was diagnosed with late-onset 21-OHD by an ACTH stimulation test. The induction of ovulation in late-onset 21-OHD patients has been with glucocorticoids. Given the success in inducing ovulation with clomiphene citrate alone in this patient with well-documented late-onset 21-OHD, it may be worthwhile to study the sole use of clomiphene citrate for ovulation induction in these patients.

17-Hydroxycorticosteroids↗
PubMed1975

LH and FSH response to synthetic LHRH after consecutive administration of clomiphene citrate in normal males.

LHRH tests (100 mug iv) were performed in 11 normal male volunteers before and after administration of 100 mg clomiphene citrate per os for 7 days. Serum FSH, both pre and post LHRH levels (peak value and area under response curve) were significantly increased (P less than 0.01) by clomiphene citrate, while the maximum increments of FSH above baseline (deltaFSH) and area under response curve from basal level (deltaarea) were unchanged. On the other hand, basal serum LH levels increased significantly (P less than 0.005), post LHRH levels did not change by clomiphene citrate, whereas the increments after LHRH administration (both deltaLH and deltaarea) decreased significantly (P less than 0.05) on the second LHRH test. Basal levels of testosterone increased following clomiphene citrate treatment (P less than 0.005). The increased testosterone is considered to suppress the effect of LHRH on LH secretion.

Administration, Oral↗
PubMed1992

Agonistic-antagonistic actions of clomiphene citrate on PGF2 alpha fluctuations in ovariectomized rat uterus.

Effects of clomiphene and/or estrogen on uterine prostaglandin (PG) F2 alpha fluctuations in ovariectomized rats were examined. Uterine PGF2 alpha fluctuations were measured at the indicated times after injection of clomiphene and/or estradiol. Antiestrogenic effects of clomiphene on urine weight and PGF2 alpha levels were observed at 6 hr, and its effect on uterine 13,14-dihydro-15-keto-PGF2 alpha forming capacity was observed at 24 hr. At 48 and 72 hr, additive effects were recognized in all parameters. These results indicate that clomiphene possesses agonistic-antagonistic actions on the PGF2 alpha fluctuations in the uterus.

Animals↗
PubMed1991

Urinary luteinizing hormone testing and prediction of ovulation in spontaneous, clomiphene citrate and human menopausal gonadotropin-stimulated cycles. A clinical evaluation.

A urinary luteinizing hormone test was utilized to predict ovulation in 99 spontaneous, 122 clomiphene citrate, and 82 human menopausal gonadotropin stimulated cycles. Tests were performed in early morning and evening specimens and follicular development was monitored by daily ultrasonography. A positive detection rate of 98, 97, and 94%, respectively, was obtained. Evidence of luteinized unruptured follicles was seen more frequently in stimulated cycles, concurring with negative test results. In 2 spontaneous, 1 clomiphene citrate and 5 hMG induced cycles two distinct LH surges were detected concomitant with a pattern of follicular atresia and subsequent new follicular development. Most ovulations occurred between 16 and 28 h after LH detection, significantly earlier in spontaneous than in clomiphene citrate stimulated cycles (p less than 0.02), whereas pre-ovulatory follicles were larger in the clomiphene citrate group (p less than 0.001). The mean duration of the follicular and luteal phases, as calculated from the LH peak, was substantially shorter in the hMG cycles than in the other two groups (p less than 0.001).

Adult↗
PubMed1980

Effects of neonatal administration of clomiphene citrate on sexual behavior of female rats: a preliminary report.

Female rats were treated with the nonsteroidal estrogen antagonist clomiphene citrate for the first 5 days postpartum. The expectation was that clomiphene would influence the sexual development of these animals as is the case with sexually immature animals treated with steroidal compounds. Analysis showed that treatment with clomiphene completely disrupted the adult sexual behavior of the female. In five consecutive days of testing the experimental females were never observed to mate. They were mounted significantly less often than controls, suggesting that the males were less attracted to them than to normal females. The initial suggestion that clomiphene might affect the sexual behavior of females has been supported; however, further research must be done to identify the underlying mechanism of the change.

Animals↗
PubMed1988

Androstenedione concentrations following dexamethasone suppression: correlation with clomiphene responsiveness in women with polycystic ovary syndrome.

It is difficult to predict clomiphene responsiveness in women with polycystic ovary syndrome (PCOS) but it has been suggested that women with evidence of excess adrenal androgen are less likely to respond to clomiphene. To investigate this further we performed a short Synacthen test following overnight dexamethasone suppression, using 11 beta-hydroxyandrostenedione (11-OHA) as a specific marker of adrenal androgen secretion in women with anovulatory infertility due to PCOS (n = 19) compared with a normal group (n = 7). Women with PCOS were subsequently divided into 2 groups according to whether or not they ovulated after clomiphene. On day 1 blood was taken at 9.00 hours for measurement of androstenedione (A), 11-OHA and cortisol, and 1 mg dexamethasone was given at 22.00 hours. On day 2 blood was taken at 9.00 hours and at 30 and 60 minutes after intravenous administration of 250 micrograms Synacthen. Before dexamethasone was given, concentrations of A but not of 11-OHA or cortisol were significantly higher in women with PCOS than in controls but there was no difference in A levels between clomiphene responders and non-responders. After 1 mg dexamethasone had been given, concentrations of A, 11-OHA and cortisol were suppressed in all 3 groups and there were no differences between the groups in the post-dexamethasone concentrations of 11-OHA or cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Amenorrhea↗
PubMed1976

Effect of melatonin on the luteinizing hormone release induced by clomiphene and luteinizing hormone-releasing hormone.

The effect of melatonin on the LH-release response after the administration of synthetic LH-RH and clomiphene citrate was investigated in adult male rats. The sc administration of melatonin (1 mg/day) for 6 days produced a significant decrease in serum LH levels and in seminal vesicles and ventral prostate weights. On the other hand, the daily injection of 0.01 mg/100 g of body weight of clomiphene citrate during 6 days significantly stimulated LH levels and the weights of the accessory sex glands. Simultaneous treatment with melatonin and clomiphene produced an inhibitory effect similar to that obtained with melatonin alone. Neither pretreatment with melatonin alone. Neither pretreatment with melatonin (1 mg/day, sc for 6 days) nor its simultaneous iv administration (500 mug) with 75 ng of LH-RH modified the LH-release in response to the hypothalamic hormone. The fact that melatonin was able to suppress the effect of clomiphene, which is probably exerted at the hypothalamic level, but not the actiion of LH-RH on the pituitary, appears to indicate that the hypothalamus may be the site involved in the inhibitory effect of the pineal principle on the reproductive function.

Animals↗
PubMed2002

[Favorable reproductive and menstrual evolution in adult women, who presented in the adolescence, menstrual disturbances by hypothalamic dysfunction and lack of response to clomiphene].

BACKGROUND: Hypothalamic dysfunction is a cause of menstrual disturbances in women, in whom other diseases have been discarded. This condition is characterized by a failure of the GNRH pulse generation system and is associated to psychological and environmental factors. A lack of ovulatory response to the administration of clomiphene can be a sign of bad prognosis in hypothalamic dysfunction. AIM: To report the natural history of patients with hypothalamic dysfunction and a bad or deficient response to the administration of clomiphene. PATIENTS AND METHODS: Fifty patients with hypothalamic dysfunction, that consulted for menstrual disturbances at the age of 15 to 20 years old, were studied. All received clomiphene and 31 had an ovulatory response, 12 had menses without ovulation and 7 did not menstruate. Of these 19 women eleven were interviewed again about their menstrual and reproductive history, after a lapse of 9 to 17 years of loss from follow up. RESULTS: Eight of the eleven women had stressful events during adolescence (going away from family house in 3, starting university studies in 3, migration out of the natal country in one and non competitive physical activity in one). All restarted their menses and eight with active sexual life had spontaneous pregnancies, giving birth from two to five children. Ovulatory cycles were documented in women without active sexual life. CONCLUSIONS: In teenagers with hypothalamic dysfunction and menstrual disturbances, a deficient or bad response to clomiphene does not necessarily indicate a bad prognosis in terms of menses or fertility.

Adolescent↗
PubMed1975

[Rat ovarian function after post or prenatal injection of clomiphen].

If newborn rats are subcutaneously injected with 0,075--0,100 mg of Clomiphene Citrate within the first 5 days, it results that 73.7% of the females remain anovulatory. The percentage rises to 100 if 0,125--0,400 mg are given in several injections. The identical treatment has no influence on the testicular function. Prenatal administration to pregnant rats (total amount 0,250--2,70 mg in repeated subcutaneous injections) interrupts the pregnancy in a high percentage, but has no effect on the later gonadal function of the foetuses. Equally ineffective is the prenatal intra-amniotic injection of clomiphene (0,125--0,250 mg into each amniotic cavity). In this respect the action of Clomiphene differs from the action of testosterone and also of estradiol, as these two hormones produce the identical effect after intra-amniotic as after postnatal administration i.e. they are effective if passage through the placenta is avoided. Clomiphene, postnatally effective, loses its effectiveness when intra-amniotically injected, although the placenta is eluded. An inactivating action of the amnion fluid could be the explanation of this phenomenon.

Abortion, Veterinary↗
PubMed2004

[Clinical observation on treatment of Stein-Leventhal syndrome caused sterility by combined use of clomiphene and Chinese nourishing shen and activating blood circulation drugs].

OBJECTIVE: To observe the efficacy of combination therapy of clomiphene and Chinese drugs for nourishing Shen and activating blood circulation (NSABC) in treating Stein-Leventhal syndrome caused sterility. METHODS: Sixty-two patients with anovulation caused sterility were randomly divided into the treated group (n = 32) and the control group (n = 30). The treated grop was treated with the combination therapy and the control group treated by the same dosage of clomiphene alone. RESULTS: After treatment, when comparing with that before treatment, the endocrine hormones in the treated group improved significantly, showing a markedly decrease of androgen and luteotropic hormone, and increase of estrogen (P < 0.001). The periodic ovulation rate in the treated group reached 87%, the total pregnancy rate being 65.6%, with no occurrence of ovarian hyperstimulation syndrome (OHSS) and luteinized unruptured follicle syndrome (LUFS), while in the control group, the periodic ovulation rate was 66%, the total pregnancy rate 36.6%, with LUFS occurred in 4 patients. Comparison of the therapeutic effects between the two groups showed significant difference (P < 0.05). CONCLUSION: The combination therapy of clomiphene and NSABC has a better therapeutic effect in treating Stein-Leventhal syndrome caused sterility than that of using clomiphene alone.

Adult↗
PubMed2004

Timing of hCG administration does not affect pregnancy rates in couples undergoing intrauterine insemination using clomiphene citrate.

BACKGROUND: Therapeutic intrauterine insemination (IUI) combined with clomiphene citrate ovarian stimulation is widely used to improve pregnancy rates for a variety of disorders. The goal of this study was to elucidate whether hCG administration at 24 or 36 hours after clomiphene citrate stimulation impacts pregnancy rates. METHODS: The study was conducted as a retrospective chart review of 182 clomiphene citrate/IUI cycles in 90 women at the Center for Reproductive Health at the University of Cincinnati Medical Center. Comparisons were made between IUls performed at 24 hours versus 36 hours after hCG. Clinical variables included age of the female partner, semen concentration and motility, and infertility diagnosis. Outcomes were pregnancy rates and live birth rates. Data analysis was performed using Chi square for proportions and Student's t-test for continuous variables. RESULTS: The pregnancy rate was 7% in the 24-hour group and 15.9% in the 36-hour group (P=0.057). However, the live birth rate was 4.0% in the 24-hour group and 8.5% in the 36-hour group (P=0.2). CONCLUSIONS: There is no significant difference in pregnancy rates in couples utilizing clomiphene citrate and undergoing IUI, whether hCG is administered at 24 hours or 36 hours prior to the procedure.

Adult↗
PubMed1977

Augmentative effect of ascorbic acid upon induction of human ovulation in clomiphene-ineffective anovulatory women.

The effect of the administration of 1-ascorbic acid, either alone or combined with clomiphene, upon induction of human ovulation was investigated in clomiphene-inffective anovulatory women. Oral administration of daily 400 mg of ascorbic acid induced ovulation in two out of five habitually anovulatory cycles and in one out of eight first-grade amenorrhea cases, and was ineffective in all six second-grade hypothalamic amenorrhea cases. Combined administration of ascorbic acid with 5 days of clomiphene induced ovulation in five out of five habitually anovulatory cycles, in 10 out of 17 first-grade hypothalamic amenorrhea cases, and in two out of nine second-grade hypothalamic amenorrhea cases. Pregnancy was established in eight out of 18 sterile, habitually-anovulatory or first-grade amenorrheic women with the combined ascorbic acid-clomiphene therapy, and in one out of five sterile, habitually anovulatory women with ascorbic acid therapy alone. Since administration of ascorbic acid induced no changed in blood FSH, LH, and amount of cervical mucus, and it is well established that LH decreases dose-dependency of the ascorbic acid content in the rat ovaries, the possible site of action of ascorbic acid seems to be at the ovarian level.

Administration, Oral↗
PubMed1986

Focal nodular hyperplasia of the liver after clomiphene treatment in a young boy.

The case of a 3.5-year-old boy treated unsuccessfully with clomiphene for cryptorchidism is reported. Nine months later focal nodular liver hyperplasia developed. Clomiphene promotes testicular descent by stimulating endogenous production of gonadotropins and their releasing factors. A causal relationship between the hepatic lesion and clomiphene treatment has been supposed. In our case subsequent fertility can only be expected from orchidopexy performed as soon as possible. Hepatic function must be checked during and after clomiphene treatment also in children.

Child, Preschool↗
PubMedDate not supplied

Tamoxifen in clomiphene-resistant hypothalamic anovulation.

Seventeen patients with clomiphene-resistant hypothalamic anovulation were given tamoxifen 10 mg per day from cycle day 5 to 9 during two consecutive menstrual cycles. Not included were patients with hyperprolactinemia and PCOD. Treatment was monitored using measurement of follicle size by ultrasound and assessment of serum estradiol. Failure to ovulate persisted in 15 patients. Of the two patients who ovulated, one received hCG on day 16, and became pregnant. We were unable to demonstrate that clomiphene-resistant patients were likely to ovulate with tamoxifen. Forty-five patients with hypothalamic anovulation not previously treated were then given tamoxifen in the same dosage. This part of the study indicated that tamoxifen was successful in inducing ovulation in 84% of the cycles. There was marked improvement in cervical mucus in tamoxifen cycles as compared with clomiphene cycles. Tamoxifen was effective, and had some advantages compared with clomiphene in patients responding to both drugs. This preliminary study suggests that tamoxifen may be a useful addition to the treatment of ovulatory failure.

Anovulation↗
PubMed1979

[Results of a long-term clomiphene citrate therapy in women with normogonadotropic menstrual disturbanes (author's transl)].

A total of 72 pregnancies was achieved in 59 women with menstrual cycle disturbances (WHO Type II) by administration of clomiphene. 27 of these pregnancies (34.7%) occurred only after more than three courses of cloimphene. A secondary classification of the patients was based on the symptomatic severity of the menstrual disturbance. Clomiphene (100 mg) was administered on the fifth day after the onset of menstruation for five days, whereby in one or two cases up to 19 courses had to be given. The group consisted of women who had rejected HMG-HCG therapy because of the possibility of multiple pregnancy. 59 pregnancies went to full term; 2 tubal pregnancies and 11 cases of miscarriage were recorded. The commencement of pregnancy was evaluated and the time of ovulation and the length of the luteal phase determined in women requiring up to three courses of clomiphene and those requiring over three courses. The investigation demonstrates that clomiphene therapy can be successful even after more than six courses of the drug. Side effects are minimal.

Adult↗