A reliable predictive test to identify perimenopausal women who are vulnerable to the adverse effects of severe estrogen deficiency may be useful in deciding for whom and when to begin estrogen replacement therapy. Primate models were employed to determine (1) whether short-term treatment with gonadotropin-releasing hormone antagonist allows prospective identification of individuals at greatest risk for a negative calcium balance during overt estrogen deficiency; (2) whether high-dose clomiphene citrate is sufficiently estrogenic to abate urinary calcium loss and to sustain vaginal and perineal tissues after ovariectomy; and (3) whether clomiphene citrate will provide these beneficial estrogenic effects without inducing endometrial proliferation and menstruation after progestin withdrawal. The data indicate the capability of short-term gonadotropin-releasing hormone-antagonist test to identify individuals likely to lose calcium rapidly after ovariectomy. This result has potential usefulness in the prediction of susceptibility to osteoporosis after medical castration or spontaneous menopause. At high doses, clomiphene citrate therapy was nearly as effective as high-dose conjugated equine estrogens for conservation of urinary calcium, yet clomiphene citrate did not cause endometrial proliferation or withdrawal bleeding after progesterone therapy.
Rafat Abbasi, Gary D. Hodgen. Predicting the Predisposition to OsteoporosisGonadotropin-Releasing Hormone Antagonist for Acute Estrogen Deficiency Test. JAMA. 1986;255(12):1600–1604. doi:10.1001/jama.1986.03370120078026