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PubMed1997

[Decreased quality of cervix mucus under the influence of clomiphene: a meta-analysis].

OBJECTIVE: To determine whether clomiphene (citrate) has a negative influence on cervical mucus qualities and whether administration of exogenous oestrogens has a favourable influence in that case. DESIGN: Meta-analysis. SETTING: Stichting Gezondheidszorg Oostelijk Zuid-Limburg, Midwifery School, Kerkrade, the Netherlands. METHOD: Relevant articles were searched using the Medline database for the years 1980-1996 and the Knowledge Finder search system. The reference lists of these articles were studied. All prospective, randomized and controlled clinical trials mentioning detailed figures were selected and analysed. RESULTS: Six articles met all criteria for analysis of the effect of clomiphene on cervical mucus. Clomiphene 50 mg/day had an unfavourable influence on cervical mucus (not significant), but clomiphene 100 and clomiphene 150 mg/day did have a significant effect, the relative risk of unfavourable cervical mucus being more than seven in comparison with women not using clomiphene (respective odds ratios 7.90 (95% confidence interval: 4.15-15.00) and 7.50 (1.97-28.60)). Four articles met all criteria for analysis of the effect of exogenous oestrogens on cervical mucus of women being treated with clomiphene. Exogenous oestrogens resulted in improvement of the cervical mucus qualities in these women (odds ratio: 2.87 (1.76-4.69)). CONCLUSION: The influence of clomiphene 50 mg/day on cervical mucus is not significantly unfavourable, unlike the influence of clomiphene 100 and 150 mg/day. Exogenous oestrogen administration improves this cervical mucus. In all patients being treated with clomiphene the cervical mucus qualities should be investigated.

Cervix Mucus↗

PubMed1977

The interaction of clomiphene, estradiol, and progesterone in the control of rat uterine glycogen metabolism.

Uterine glycogen accumulation was studied in ovariectomized rats treated with all combinations of clomiphene citrate (0.25 mg/kg) estradiol (1.0 micron g) and progesterone (5.0 mg). The rats were given three consecutive daily dosages and killed 24 hours after the final dosage. Based on biochemical data, either estradiol or clomiphene increased uterine glycogen concentration and total glycogen, but progesterone did not. Progesterone significantly suppressed both the estradiol and clomiphene-induced glycogen increases. Based on the histochemical results, progesterone also suppressed the estradiol and clomiphene-induced glycogen responses, but the tissue affected differed. Clomiphene markedly increased luminal epithelial glycogen whereas estradiol induced primarily myometrial glycogenesis. Progesterone completely suppressed the clomiphene-induced epithelial effect and partially suppressed the estradiol-induced myometrial effect. Clomiphene also suppressed the estradiol-induced myometrial response. The results indicate that progesterone does have a significant interaction with clomiphene in the control of uterine morphology and biochemistry. The results also stress the importance of correlated histochemical and biochemical studies in the study of clomiphene-induced uterine glycognesis.

Animals↗

PubMed2000

Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea.

BACKGROUND: The administration of clomiphene citrate is followed by an enhanced release of pituitary gonadotropins resulting in follicular recruitment. After the drug is stopped, there is continuing secretion of estradiol, selection of the dominant follicle and, in successful cases, ovulation. Clomiphene is indicated as the initial treatment in the majority of women with amenorrhoea and oligomennorhoea. In women with irregular ovulation it seems to re-establish typical frequency of ovulation. Its effectiveness in oligo-amenorrhoeic women was tested in a number of randomized controlled trials at that time. These trials form the basis for the following review. OBJECTIVES: Clomiphene citrate enhances the release of pituitary hormones, often resulting in ovulation. The objective of this review was to assess the effects of clomiphene citrate on ovulation and pregnancy in women with oligo-ovulatory subfertility. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: Randomised trials of clomiphene compared with placebo or no treatment in women with oligo-ovulatory subfertility of at least 12 months duration. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Four studies were included. They were all of crossover design. Since it was not possible to separate data from the first and second phases of these trials, the effect of clomiphene may be overestimated. Compared with placebo, clomiphene citrate was associated with increased ovulation. The odds ratio for high doses (50-250 milligrams per day) was 6.82 (95% confidence interval 3.92 to 11.85). This dropped to a non-significant odds ratio of 1.29 (95% confidence interval 0.48 to 3.49) with low doses (10 milligrams per day). Clomiphene citrate (all doses) was associated with an increased pregnancy rate per treatment cycle (odds ratio 3.41, 95% confidence interval 4.23 to 9.48). REVIEWER'S CONCLUSIONS: Clomiphene citrate (at doses between 50 to 250 milligrams per day) appears to be an effective method of inducing ovulation and improving fertility in oligo-ovulatory women. However adverse effects include possible ovarian cancer risk and risk of multiple pregnancy.

Amenorrhea↗

PubMedDate not supplied

Clomiphene citrate and ovulation induction.

Clomiphene can be used to treat anovulation due to hypothalamus or pituitary gland dysfunction, and it normalizes the luteal phase in stimulated patients. It can be used to estimate ovarian follicle reserve, and may be predictive of ovulation in women aged >/=35 years or with failed IVF. Contraindications include risk of congenital anomalies, chronic liver disease and visual disorders. Clomiphene may impair fertility through its effects on cervical mucus and in causing various endometrial dysfunctions. However, if clomiphene is administered in 50 mg doses, side-effects are avoided and efficacy is similar to that of a 100 mg dose, although daily dosages of 200 mg/day over 5 days can induce ovulation in approximately 70% of treated patients. Gonadotrophin concentrations increase up to days 5-9 when follicles are selected, and clomiphene is effective in patients with polycystic ovary syndrome (PCOS). Fifty percent of normal patients conceive, a value perhaps biased by the antagonistic effects of clomiphene on cervical mucus in some women. Clomiphene is valuable for IVF, and is used by some clinics in combination with HMG or recombinant FSH. Resistance to clomiphene can develop, and human chorionic gonadotrophin may be needed to induce ovulation in clomiphene cycles. Corticosteroids and human menopausal gonadotrophin (HMG) can be combined with clomiphene for stimulation, its combination with HMG long having been a standard protocol in assisted reproduction. PCOS patients may become insulin resistant, a condition improved by the administration of metformin. Other adverse effects include multiple pregnancies, an increase in the rate of multiple births, ovarian hyperstimulation and unsubstantiated claims of ovarian cancer.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Modern use of clomiphene citrate in induction of ovulation.

Clomiphene citrate is the treatment of first choice in the management of infertility in normally oestrogenized, anovulatory women (WHO group II). The majority of women with 'pure' anovulatory infertility respond to treatment with clomiphene citrate. The rates of pregnancy and miscarriage are close to those expected in a normal fertile population. Basal hormone concentrations do not predict outcome. An increased body mass index is the only factor which is consistently associated with a decreased response to clomiphene citrate; it follows therefore, that weight reduction should be an important part of therapy in anovulatory women. According to our data, only an increased luteinizing hormone value immediately post clomiphene citrate predicted an adverse pregnancy outcome in women who conceived. Clomiphene citrate, along with other ovulation induction therapies, can cause multiple follicular development, with a risk of ovarian hyperstimulation and multiple pregnancy. Ultrasound monitoring of treatment is important in order to choose the appropriate dose of clomiphene citrate in subsequent cycles and to minimize the risks of hyperstimulation and multiple pregnancy. When couples with other factors contributing to subfertility are excluded, the cumulative conception rate continues to rise after 6 months of treatment with clomiphene citrate, reaches a plateau by treatment cycle 12 and approaches that of the normal population. It has been reported that prolonged use of clomiphene citrate may be associated with an increased risk of a borderline or invasive ovarian tumour. Taking into consideration these observations, we recommend that anovulatory women responsive to clomiphene citrate should be treated for at least 6 cycles before considering more complex or invasive methods of ovulation induction, and that treatment should probably be limited to a maximum of 12 cycles.

Adult↗

PubMed1989

A comparison of the effects on follicular development between clomiphene citrate, its two separate isomers and spontaneous cycles.

An investigation of the effects on follicular development of clomiphene citrate and its two isomers En clomiphene and Zu clomiphene given separately was carried out on 19 normally cycling women being treated with donor insemination. All women received clomiphene citrate in the first cycle and, following a washout control cycle, were treated with either En clomiphene or Zu clomiphene alone. The number of follicles present, follicular phase oestrogen secretion and luteal phase pregnanediol excretion were not significantly different when Zu clomiphene cycles were compared with control cycles, but were significantly increased in En clomiphene and clomiphene citrate cycles. It is concluded that the En isomer, which has largely antioestrogenic properties, is the isomer active in inducing follicular development. The oestrogenic properties of Zu isomer did not appear to protect it from the possibly detrimental effects on sperm-cervical mucus interaction observed in both isomers and in the combined preparation.

Adult↗

PubMed1990

Effect of clomiphene isomers on oestradiol synthesis in cultured human granulosa cells.

The effects of en-clomiphene and zu-clomiphene (10(-7) - 10(-5) M) on oestradiol synthesis in human granulosa cells were studied. Granulosa cells were obtained from stimulated cycles in women undergoing oocyte retrieval, in the course of in-vitro fertilization/embryo transfer due to mechanical infertility. En-clomiphene and zu-clomiphene (10(-5) M) significantly reduced basal and LH-stimulated oestradiol synthesis after 2-4 days of culture. The LH-stimulated synthesis was also significantly and reversibly reduced by zu-clomiphene at lower concentrations (10(-6) - 10(-7) M) and by a mixture of en- and zu-clomiphene (10(-6) M). It is concluded that both the mixture of en- and zu-clomiphene and the isomers alone have direct inhibitory effects on oestradiol synthesis in human granulosa cells in vitro. Furthermore, it cannot be excluded that the LH-stimulated oestradiol synthesis is inhibited by zu-clomiphene at concentrations found in follicular fluid after administration of clomiphene citrate.

Cells, Cultured↗

PubMed1992

Increased pregnancy failure rates after clomiphene following assisted reproductive technology.

The obstetric outcome of 1941 in-vitro fertilization (IVF) and 1436 gamete intra-Fallopian transfer (GIFT) pregnancies reported from 25 units in Australia and New Zealand have been reviewed. Recently, gonadotrophin-releasing hormone analogues (GnRHa) have replaced clomiphene as part of many ovarian stimulation protocols. Clinical abortion rates after clomiphene (24.4% for IVF; 23.0% for GIFT) were not significantly higher than after GnRHa (20.7% for IVF; 17.9% for GIFT) when IVF and GIFT data were considered separately. However, the abortion rate for combined IVF and GIFT was significantly higher after clomiphene than after GnRHa. This pattern was found for most maternal age groups and causes of infertility although differences were not significant in all categories. The combined IVF and GIFT ectopic pregnancy rate of 6.7% for clomiphene was significantly higher than 4.1% for GnRHa. Because the mechanism of action of clomiphene for oocyte recruitment during folliculogenesis means that GnRHa cannot be used with clomiphene, luteinizing hormone (LH) levels are higher in clomiphene cycles than in GnRHa cycles. Clomiphene itself could cause the increase in pregnancy wastage or increased levels of LH during follicule genesis associated with the use of clomiphene may cause the observed pregnancy failures.

Abortion, Spontaneous↗

PubMed1981

Cyclic clomiphene citrate treatment lowers cytosol estrogen and progestin receptor concentrations in the endometrium of postmenopausal women on estrogen replacement therapy.

Clinical and experimental studies have indicated that a nonsteroidal antiestrogen, clomiphene citrate, might prevent the stimulatory action of estrogens on the human endometrium. To investigate the mechanisms of this effect, the treatment of 19 postmenopausal patients with conjugated estrogens for 6 months was supplemented cyclically for 10 days with clomiphene citrate after every 7 weeks. Ten patients ingested clomiphene citrate alone, whereas 9 patients continued estrogen treatment during clomiphene supplementation. Estrogen and progestin receptors were measured from the cytosol of the endometrium after the first estrogen period and after the first and third clomiphene treatment. The estrogen receptor concentration was significantly lower after both clomiphene supplementation periods than after the initial estrogen administration. The progestin receptor concentration was significantly lower only after the first clomiphene citrate period. The effect of clomiphene citrate was independent of the initial histological appearance of the endometrium and led to atrophy of the endometrium in most of the patients. Because the effect of clomiphene citrate was independent of simultaneous estrogen administration, it acted as a pure antiestrogen in this treatment modality. The relative decreases in estrogen and progestin receptor concentrations on the present treatment regimen were different from those previously found on progestin treatment and most likely occur via different mechanisms. It is not known whether these two treatment types will have additive effects.

Clomiphene↗

PubMed1981

Dose- and age-dependent effects of clomiphene citrate administered to prepubertal female rats on development of anovulatory sterility and pyosalpinx.

The influences of dose of clomiphene and age at clomiphene treatment in prepubertal female rats on development of anovulatory sterility and pyosalpinx were investigated. By varying the amount of clomiphene administered, it was found that 50 micrograms is the minimal dose of clomiphene which will produce anovulatory sterility and pyosalpinx in a majority of female rats treated at 5 days of age. By varying the age of rats at clomiphene treatment, it was observed that the period of clomiphene sensitivity in female rats is within the first 10 days of life, in which administration of 500 micrograms clomiphene will result in subsequent anovulatory sterility and pyosalpinx. These results demonstrate that the induction of anovulatory sterility and pyosalpinx is dependent upon the dose of clomiphene and the age of rats at clomiphene injection.

Age Factors↗

PubMed1981

Time-related effects of en-clomiphene upon central and peripheral oestrogen target tissues and cytoplasmic receptors.

The temporal effects of the oestrogen antagonist en-clomiphene were studied in the 3 week ovariectomized rat for up to 24 days after a single dose of 0.5 or 50 mg/kg. Cytosol binding of [3H]oestradiol was measured in central and peripheral target tissues. One day after treatment both doses of en-clomiphene decreased binding of [3H]oestradiol to similar levels within tissues. In brain cytosols binding of [3H]oestradiol returned to expected control values by 16 days with the exception of the hypothalamic cytosol after treatment with 50 mg/kg which, paradoxically, achieved control levels by 8 days. However, a single-point saturation assay was inadequate for the measurement of high-affinity oestrogen receptors in brain tissue. Uterine binding of [3H]oestradiol returned to control levels by 2 and 16 days after treatment with 0.5 and 50 mg/kg respectively. Replenishment of [3H]oestradiol binding was slower in pituitary cytosol and was achieved by 8 and 24 days after treatment with 0.5 and 50 mg/kg respectively. En-clomiphene was uterotrophic; the maximal increase was at 4 days and 1 day after 0.5 and 50 mg/kg and was sustained, albeit at a lower level, for 4 and 8 days respectively. En-clomiphene at 50 mg/kg increased total uterine DNA 2 days after treatment. Small dose-related sustained increases in weight of uterine luminal fluid were also observed. En-clomiphene had no effect upon serum FSH. Serum LH was decreased only on day 8 after treatment. Serum prolactin was increased to a similar level by both doses of en-clomiphene; however, the maximum was achieved 2 and 16 days after treatment with 0.5 and 50 mg/kg respectively. Rats were tested for sexual receptivity after 50 mg/kg en-clomiphene and increases were detected between 7 and 9 days of treatment. Progesterone facilitated this effect only on days 8 and 9. En-clomiphene produced dose-related falls in food intake and body weight, the latter remaining below the weights of control rats throughout the period studied. It is apparent that the temporal effects of en-clomiphene upon cytoplasmic [3H]oestradiol binding are diverse, replenishment of binding being dependent upon the dose and the tissue examined. In addition, the changes in biological activity as measured by uterine and neuroendocrine effects also appear temporally unrelated to each other and to the binding of [3H]oestradiol. Thus further studies are necessary to elucidate possible differences in tissue oestrogen receptor mechanisms and the mode of action of the oestrogen antagonists.

Animals↗

PubMed1982

[Evaluation of hypothalamic-pituitary function in amenorrheic women by utilizing the combined clomiphene-GnRH test (author's transl)].

Hypothalamic-pituitary function in 62 women with amenorrhea syndrome was evaluated by comparing the response of gonadotropin to GnRH stimulation before and after clomiphene treatment. Each woman was initially tested with an intramuscular injection of 100 microgram GnRH, and then ingested 150 mg of clomiphene daily for 5 consecutive days followed by GnRH test. Fourteen out of 29 patients with 1st grade amenorrhea showed increased baseline LH, FSH and estradiol, and slightly decreased net responses of LH to GnRH after clomiphene administration, indicating that positive and negative estrogen feedback for gonadotropin release is functioning. In contrast, 8 patients with 2nd grade amenorrhea (17 cases) showed an increase in LH net responses after Clomid treatment. In 5 patients, however, clomiphene induced the increase in baseline LH and FSH values and the decrease in the LH release in response to GnRH as seen in the 1st grade amenorrheic patients. These 5 patients ovulated on that clomiphene dosage. One patient with PCO also had a barely significant decrease in LH responses to GnRH following clomiphene administration, with slightly increased baseline gonadotropins. With one exception, all the 5 patients with primary amenorrhea showed no or poor LH responses to GnRH. Following clomiphene administration, no change in either baseline gonadotropine levels or pituitary responsiveness to GnRH was observed in 4 patients, suggesting that a hypothalamic-pituitary defect appeared most likely to be present. The two patients with streak gonad had significantly high responses to GnRH injection and further increase in the responses following clomiphene administration, accompanied by a slightly decreased baseline gonadotropin levels. On the other hand, in hyperprolactinemic amenorrhea syndrome individual response to GnRH before and after clomiphene use was quite variable. It is likely that this group includes the patients with various pathologic states of the hypothalamic-pituitary system. Thus, syndrome and in diagnosing the degree and the site of the defect.

Adolescent↗

PubMed1991

Preventive effects of clomiphene citrate on estrogen-deficiency osteopenia elicited by LHRH agonist administration in the rat.

The estrogen agonist and antagonist clomiphene citrate has been shown to prevent bone loss induced by ovariectomy in the rat. In young women estrogen-deficiency bone loss is a clinical problem associated with the use of luteinizing hormone releasing hormone (LHRH) agonists, such as buserelin, to treat endometriosis. The aim of this study was to determine whether clomiphene citrate (10 mg/kg body weight per week orally) would prevent the osteopenic effect of buserelin (25 micrograms/kg body weight per day SC) in the rat. Four groups of animals with 45Ca-labeled skeletons were studied for 4 weeks: group A, placebo controls; group B, buserelin; group C, clomiphene; and group D, buserelin + clomiphene. Bone resorption was monitored by measuring the urinary excretion of 45Ca and hydroxyproline. Clomiphene slowed bone breakdown and inhibited the osteopenic effect of buserelin. Total-body calcium values (mean +/- SD) were (mg) 2635 +/- 181, 2267 +/- 85, 2566 +/- 126, and 2624 +/- 77 in groups A to D, respectively. Osteopenia was present only in group B (P less than 0.001). Interestingly buserelin lowered blood 17 beta-estradiol and uterine weights to a similar extent in the presence and absence of clomiphene. Because clomiphene inhibited estrogen-deficiency bone loss in buserelin-treated rats without depressing the hypoestrogenic action of this LHRH agonist, it is suggested that the use of clomiphene to protect the skeleton during LHRH agonist therapy of endometriosis warrants further study.

Animals↗

PubMed1984

Induction of luteal phase defect with clomiphene citrate.

The effect of clomiphene citrate and progesterone on luteal function in infertile women was studied. Endometrial biopsies were performed in 103 women immediately prior to menstruation. Group 1 (n = 62) had secretory endometrium with a histologic lag time of greater than or equal to 48 hours with respect to the subsequent menses, that is, luteal phase defect. Group 2 (n = 10) had normal histologic characteristics of the secretory phase. Group 3 (n = 31) had anovulatory endometrium. The last group was subdivided into those with polycystic ovary syndrome (n = 9) and those without the characteristic gonadotropin pattern of polycystic ovary syndrome (n = 22). Clomiphene citrate at doses of 50 to 250 mg daily for 5 days was administered for induction of ovulation, timing of ovulation, or treatment of luteal phase defect. An endometrial biopsy was obtained after three ovulatory treatment cycles. Only one fourth of the women with prior luteal phase defect had normalization of the biopsy specimen with clomiphene citrate, while one half of those treated with progesterone had normal specimens. Half of the normally ovulating women had induction of a luteal phase defect with clomiphene citrate. Only women with polycystic ovary syndrome had consistently well-timed endometrial histologic features with clomiphene citrate therapy. Despite successful induction of ovulation, 16 of the other 22 previously anovulatory women had endometrial histologic findings compatible with luteal phase defect. Increasing the clomiphene citrate dosage was unsuccessful in improving endometrial maturation. These results suggest that the use of clomiphene citrate may be associated with a high rate of luteal phase defect induction, except among women with polycystic ovary syndrome. Clomiphene citrate, even at high doses, appears to be ineffective therapy for luteal phase defect.

Anovulation↗

PubMed1987

Effect of clomiphene citrate administration during the early luteal phase on the luteal function and pregnancy rate of women.

To study the effect of clomiphene citrate (clomiphene) administration during the early luteal phase of the menstrual cycle on the luteal function and the pregnancy rate in women, 75 infertile women who ovulated but did not conceive after clomiphene treatment during the early follicular phase and 6 normal cycling women were chosen. Clomiphene was administered orally to 35 of the 75 infertile women at a dose of 50 mg per day for 5 days from the second day of the rise in the basal body temperature (BBT) as well as during the follicular phase, while 40 control patients received clomiphene only during the follicular phase. In the test patients, the rate of pregnancy (25.7%) was significantly (p less than 0.05) higher than that of control patients (10.0%). On the 7th of the rise of BBT, the mean serum progesterone levels of the test patients and normal cycling women treated with clomiphene were significantly (p less than 0.05) higher than those of the control patients. However, the levels of serum estradiol, LH and FSH, the gonadotropin pulsatilities, and the pituitary responses to LH-RH in the test women were not significantly different from those of the control. These data suggest that, when administered during the early luteal phase, clomiphene may act directly on the ovary, enhancing the secretion of progesterone from the corpus luteum, and thereby increasing the rate of pregnancy in infertile women with clomiphene-induced ovulation.

Adult↗

PubMedDate not supplied

Alcoholic hypogonadism: hormonal response to clomiphene.

To investigate the androgen, weak androgen, estrogen, and gonadotrophin response to clomiphene in alcoholics, we determined in 63 male patients (25 with and 38 without liver cirrhosis) serum testosterone, sexual hormone binding protein (SHBG), dehidroepiandrosterone, androstenedione, LH, FSH, prolactin, and estradiol levels, on the first and the sixth day after admission, and after a course of 8 days of clomiphene 200 mg/day. The same test was performed on 15 healthy volunteers. Cirrhotic patients showed decreased basal testosterone levels and a loss of the circadian rhythm with recovery after clomiphene. Although basal testosterone levels in noncirrhotic alcoholics did not differ from those of the controls, there was a significant improvement after withdrawal. SHBG levels were higher in both groups of alcoholics than in controls, pointing to a worse degree of hypogonadism, because only the free hormone is active. Before the clomiphene test, serum LH and FSH levels were nonsignificantly higher in both groups of alcoholics than in the control group. After clomiphene both LH and FSH increased. Androstenedione and estradiol showed a (parallelism) similar behavior in alcoholic and in cirrhotic groups, showing in both cases higher levels than in the control group, and an increase after clomiphene, perhaps reflecting peripheral conversion of androgens to estrogens. Because clomiphene has no effect on the adrenal cortex, the increase of androstenedione after clomiphene points to its testicular origin (directly or after testosterone conversion) and not to an adrenal one. The highest serum estradiol levels were observed in cirrhotics with ascites or gynecomastia. We have not found any relation between serum hormone levels and alcohol intake nor with nutritional status.

Adult↗

PubMed2001

Inhibition of volume-regulated anion channels in cultured endothelial cells by the anti-oestrogens clomiphene and nafoxidine.

1. We have used the whole-cell patch clamp technique to study the effect of the partial anti-oestrogens clomiphene and nafoxidine, the pure anti-oestrogens ICI 182,780 and RU 58,668 and the oestrogen ss-estradiol, on the volume-regulated anion channel (VRAC) in cultured pulmonary artery endothelial (CPAE) cells. 2. In contrast to the pure anti-oestrogens and ss-estradiol, clomiphene and nafoxidine potently inhibited the volume-sensitive chloride current, I(Cl,swell), activated by challenging CPAE cells with a 25% hypotonic solution. For clomiphene, the estimated IC(50) and Hill coefficient were 1.03+/-0.14 microM and 1.40+/-0.21 respectively. In the case of nafoxidine, these values were 1.61+/-0.29 microM and 1.24+/-0.19. 3. The inhibition induced by the pure enantiomers of clomiphene, zuclomiphene and enclomiphene, was not different from that of the racemic mixture, indicating that the interaction between clomiphene and VRAC is not stereoselective. 4. Clomiphene and nafoxidine inhibited proliferation of CPAE cells. Half-maximal inhibition was found at 1.98+/-0.17 and 1.66+/-0.21 microM respectively, concentrations similar to those for half-maximal block of VRAC. 5. In conclusion, the nonsteroidal partial anti-oestrogens nafoxidine and clomiphene are potent inhibitors of volume-regulated anion channels. The inhibition by clomiphene is not stereoselective and occurs at concentrations close to therapeutically relevant concentrations. Finally, both drugs inhibit the proliferation of endothelial cells.

Cell Division↗

PubMed1999

High ovulatory rates with use of troglitazone in clomiphene-resistant women with polycystic ovary syndrome.

This preliminary report reviews our experience with 18 infertile patients with clomiphene-resistant polycystic ovary syndrome (PCOS). In the first treatment cycle, troglitazone was administered alone. During cycles 2-5, clomiphene was added with increments of 50 mg (up to 200 mg/day) if the previous cycle was anovulatory. Basal body temperature charts and serum progesterone were obtained to confirm ovulation. In a total of 66 treatment cycles, ovulation occurred in 44 (67%) and pregnancy in seven (11%). There were no significant changes in body weight, waist:hip ratio or liver enzymes during treatment. Troglitazone, alone or with clomiphene, induced ovulation in 15 of 18 patients (83%) and seven (39%) of them achieved pregnancy. This is the first report on ovulatory rates in clomiphene-resistant women with PCOS when troglitazone was used alone or with clomiphene. Recently, metformin and clomiphene were successfully used in women with PCOS. However, our patients represent a more resistant population of women with PCOS, with each patient serving as her own historical control by previous resistance to clomiphene. Although the pregnancy rate (39%) was promising for clomiphene-resistant women with polycystic ovary syndrome, it does not seem to have a definite advantage over gonadotrophins.

Adult↗