Effect of Clomiphene on the Uptake of Estradiol by the Anterior Hypothalamus and Hypophysis

Kato, Junzo; Kobayashi, Takashi; Villee, Claude A.

doi:10.1210/endo-82-5-1049

Cited by 99 publications

(32 citation statements)

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“…The results of this study support the opinion that the hypothalamic-pituitary portion being the primary action site of clomiphene (Igarashi et al, 1967;Kato et al, 1968;Roy et al, 1964;Schally et al, 1970;Seki et al, 1972 b) as in those who responded to clomiphene an early elevation of gonadotropin(s) appeared during or immediately after administration of clomiphene.…”

Section: ) Corpus Luteum Insufficiencysupporting

confidence: 87%

Evaluation of Serum FSH and LH in Various Infertile Women Treated with Clomiphene Citrate

Huang

1972

Endocrinol Japon

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and Taiwan Provincial Chiayi Hospital, Chiayi, Taiwan Synopsis Serum FSH and LH levels were measured serially by radioimmunoassay in fifteen menstrual disordered or infertile subjects for two menstrual cycles, one control cycle and another cycle treated with clomiphene citrate. Lack of normal cyclic patterns that usually appear in ovulatory individuals of serum FSH and LH, however, within the range of normal levels in most subjects, as well as the day-to-day fluctuation of gonadotropin levels were observed in amenorrheic or anovulatory patients. By regarding the early rise of gonadotropins after clomiphene intake as a favorable response, those with fluctuating gonadotropin levels during untreated cycle were found to respond considerably to clomiphene citrate. Thus, a predictability is suggested. In the clomiphene-induced ovulatory cycles the serum FSH and LH exhibited either similar to those usually seen in normal ovulatory cycle or without a sequence of normal pattern but midcycle surge. The discordancy of gonadotropins stimulated by clomiphene which suggested the cause of temporal failure with this medicine was pointed out.

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Section: ) Corpus Luteum Insufficiencysupporting

confidence: 87%

Evaluation of Serum FSH and LH in Various Infertile Women Treated with Clomiphene Citrate

Huang

1972

Endocrinol Japon

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“…In comparison with many ivestigations of the anti-estrogenic effect of the compound (Igarashi et al, 1967 ;Kato et al, 1968;Kastin et al, 1970;Vaitukaitis et al, 1971 ;Vandenberg and Yen, 1973), the intrinsic estrogenic effect has not been well examined, especially on the hypothalamus or pituitary gland, although Czygan and Schulz (1972) presented data on the suppression of serum LH and FSH with clomiphene citrate in postmenopausal women. Our results confirm the observations of these authors.…”

Section: Discussionmentioning

confidence: 99%

“…The anti-estrogenic effect of clomiphene has been extensively investigated and well documented (Igarashi et al, 1967;Kato et al, 1968 ;Kastin et al, 1970).…”

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confidence: 99%

Dual effect of clomiphene citrate on pituitary gonadotropin secretion in postmenopausal women.

et al. 1976

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SynopsisFifteen postmenopausal women were given 25mg, 50mg of clomiphene citrate daily by mouth for 3 consecutive days. Significant (p<0.01) decrease of serum LH (73%, 65%) and FSH (76%, 76%) resulted after administration of 25mg and 50mg clomiphene citrate respectively.The suppressive effect was sustained for at least 4 days after cessation of this drug.On the other hand decreased LH and FSH levels after administration of ethinyl estradiol increased again by simultaneous administration of clomiphene citrate. These results suggest that estrogenic effects of clomiphene citrate are observed in untreated estrogen deficient subjects but anti-estrogenic effects are evident when serum estrogen levels are restored in subjects with estrogen deficiency.Clomiphene citrate is a derivative of the synthetic estrogen TACE (chlorotrianisene) and promotes LH and FSH release by its anti-estrogenic effect (Vaitukaitis et al., 1971;Vandenberg and Yen, 1973). The anti-estrogenic effect of clomiphene has been extensively investigated and well documented (Igarashi et al., 1967;Kato et al., 1968 ;Kastin et al., 1970).On the other hand, clomiphene citrate has been found to possess weak estrogenic effects on peripheral tissue (Coppola and Perrine, 1965 ;Roy et al., 1964) and in sexual behavior in rats (Ross et al., 1973). However few systematic studies have been published concerning the estrogenic effect of clomiphene citrate of hypothalamus or pituitary gland, although Czygan and Schulz (1972) have reported inhibitory effect of the drug on LH and FSH release in postmenopausal women.Our study was so carried out as to ascertain the estrogenic and anti-estrogenic effects of this compound on hypothalamus or pituitary gland in nostmenonausal women. Materials and Methods SubjectsFifteen postmenopausal women, aged 52-66 years, without clinical evidence of disease, from whom informed consent had been obtained were given 25mg, 50mg of clomiphene citrate daily by mouth for 3 consecutive days. Three subjects received different doses of clomiphene citrate on different occasions, more than one month apart, in order to study the dose-related response.Three subjects. were given 0.1mg of ethinyl estradiol alone for 5 days, and 3 weeks later, when the decreased basal gonadotropin levels returned, the same dosage of ethinyl estradiol was given to the same subjects for 5 days with simultaneous administration of 200mg clomiphene citrate from the 3rd day. MethodsSerum LH and FSH were measured by radioimmunoassay method as described elsewhere (Hashi-

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“…Clomiphene citrate is a synthetic nonsteroidal com pound with a weak estrogen activity which behaves as a potent antiestrogen agent in man, since its main function is to compete for estrogen receptors in the hypothalamus and pituitary gland [24,25]. This interaction neutralizes the negative feedback control of estrogens resulting in a rise of LH and FSH secretion [26] and subsequently inducing an increase in testosterone and sperm production by the testis [24,27], This characteristic allows us to use this drug to investigate the integrity of the gonodal axis in men [28].…”

Section: Discussionmentioning

confidence: 99%

Effect of Clomiphene Citrate on Hormonal Profile in Male Hemodialysis and Kidney Transplant Patients

Martín‐Malo

Benito

Castillo

et al. 1993

Nephron

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The aim of this study was to evaluate the role of clomiphene citrate (CC) therapy in the hypothalamus-pituitary-gonadal axis of male uremic subjects. Thirty-four patients on hemodialysis (HD) and 8 successful kidney transplant subjects (RT) were evaluated. Nine healthy males were used as controls (C). At baseline, zinc, testosterone (TEST), prolactin (PRL), FSH, LH and estradiol plasma concentrations were measured. All subjects were treated with CC (100 mg/day) for a week. The aforementioned parameters were determined again on the seventh day of CC therapy, and 3 days after drug withdrawal. Following CC, there was a rise in FSH, LH and TEST levels in all subjects (p < 0.05); it is interesting to stress that TEST became normal in HD. In addition, we observed a decrease of PRL after CC only in HD patients (p < 0.01). In summary, CC was able to partially correct most of the hormonal disturbances of the gonadal axis in uremic patients.

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Effect of Clomiphene on the Uptake of Estradiol by the Anterior Hypothalamus and Hypophysis

Cited by 99 publications

References 0 publications

Evaluation of Serum FSH and LH in Various Infertile Women Treated with Clomiphene Citrate

Evaluation of Serum FSH and LH in Various Infertile Women Treated with Clomiphene Citrate

Dual effect of clomiphene citrate on pituitary gonadotropin secretion in postmenopausal women.

Effect of Clomiphene Citrate on Hormonal Profile in Male Hemodialysis and Kidney Transplant Patients

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