Antiestrogenic action of high-dose clomiphene in primates pituitary augmentation but with ovarian attenuation.

Abstract:

:Since the dominant follicle is selected by days 5 to 7 of the menstrual cycle, we assessed the differential effects of high-dose clomiphene (25 mg daily) by giving 5-day courses either before (days 1 to 5), during (days 5 to 9), or after (days 9 to 13) emergence of the selected dominant follicle in monkeys. Peripheral sera were obtained daily and assayed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-estradiol (E2), and progesterone (P); serial laparoscopies were performed. Rather than enhancement of gonadotropin-dependent folliculogenesis during clomiphene treatment cycles, ovulation was delayed in 18 of 18 treatment cycles. Interestingly, the interval from treatment to next ovulation lengthened when clomiphene was given in the late follicular phase. Consistently, the clomiphene treatment cycles were characterized by a marked decline of the serum E2 during the 5 days of therapy, despite concurrent elevations of pituitary gonadotropins in circulation, especially FSH. These data suggest that a direct antiestrogenic effect of clomiphene imparted ovarian refractoriness to the prevailing, even enhanced, gonadotropin levels. The vulnerability of follicular maturation to these attenuating effects of clomiphene was greatest in the late follicular phase, well after the dominant follicle had been selected. Even after this clomiphene-induced ovarian hiatus and eventual resumption of new follicle growth, the initial apparent ovulation led to latent, severe corpus luteum insufficiency.

journal_name

Fertil Steril

journal_title

Fertility and sterility

authors

Marut EL,Hodgen GD

doi

10.1016/s0015-0282(16)46403-4

subject

Has Abstract

pub_date

1982-07-01 00:00:00

pages

100-4

issue

1

eissn

0015-0282

issn

1556-5653

pii

S0015-0282(16)46403-4

journal_volume

38

pub_type

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