Abstract
The following observations in 41 women and 15 men receiving clomiphene citrate illustrate its effects and imply a primary mechanism of action.Antiestrogenic effects. Vaginal cornification, cervical mucus arborization, and endometrial growth were inhibited. These effects were related to the dose and duration of therapy. Hot flushes occurred in 13 of 33 women with functioning ovaries. Amelioration of fibrocystic mastitis resulted in each of 5 patients treated.Estrogenic effects. In estrogen-deficient women, hot flushes and gonadotropin titers were decreased.Gonadotropin stimulating effects. In an estrogen-treated patient with Turner's syndrome, the suppressed gonadotropin secretion was increased.In all male patients with normal urinary gonadotropins,FSH andLH increased proportionately, in females, total gonadotropin excretion increased in 4 and decreased in 1 patient.The titer was increased in 1 of 2 patients with reduced excretion of gonadotropins, and decreased in the other. In 3 patients without urinary gonadotropins, no change was observed.Gonadal stimulating effects. A moderate to marked increase in sperm counts was observed in 10 out of 11 oligospermic males.In 25 anovulatory women, ovulation was induced in 35 of 77 cycles. Regular ovulation was induced in 7 patients in whom it was previously irregular.Urinary neutral 17-ketosteroids increased in 5 males with normal titers of gonadotropins. No definite increase was found in 3 gonadotropin-deficient males or in any of the female patients.These data are interpreted to indicate that clomiphene citrate, a weak estrogen, inhibits the effects of endogenous estrogen at the cellular level, which produces a reflex hypersecretion of gonadotropin and consequent gonadal stimulation.
Published Version
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