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Recovery of Hormone Secretion after Chronic Gonadotropin-Releasing Hormone Agonist Administration in Women with Polycystic Ovarian Disease^*

DOMINIQUE DE ZIEGLER, KENNETH STEINGOLD, MARCELLE CEDARS, JOHN K. H. LU, DAVID R. MELDRUM, M.D., HOWARD L. JUDD, M.D. and R. JEFFREY CHANG^|

Departments of Obstetrics and Gynecology, University of California School of Medicine Los Angeles, California 90024

Persistent suppression of gonadotropin and ovarian steroid production can be achieved in women with polycystic ovarian disease (PCO) by daily administration of a long-acting GnRH agonist (GnRHa). This study was designed to determine the patterns of recovery of clinical responses and hormonal secretion after chronic GnRHa administration in women with PCO. Six women with PCO were treated with daily sc injections of [D-His⁶(imBzl),Pro⁹-NEt]GnRHa (100 µg) for 6 months. Blood samples were obtained at the time of and three times weekly for 90 days after discontinuation of agonist therapy. In five women who did not ovulate, the suppressed serum FSH levels rose to pretreatment values within 10 days. In contrast, a gradual and progressive increase in serum LH (as measured by bioassay and immunoassay) was apparent by day 18. The LH increase coincided with progressive increases in serum estrone (E₁), androstenedione, and testosterone. Serum estradiol (E₂) began to rise on day 28. All hormones returned to their pretreatment baseline values within the 90-day recovery interval, with the exception of E₂. Trend analysis of the slopes of recovery revealed that the incremental secretion patterns of E₁, E₂, androstenedione, and testosterone differed significantly from that of FSH, but not from those of bioactive or immunoactive LH. Serum progesterone, dehydroepiandrosterone sulfate, and cortisol did not change after withdrawal of GnRHa. One woman ovulated spontaneously on day 52 before which her hormone secretion patterns were indistinguishable from those of the other women. In summary, 1) during recovery after discontinuation of chronic GnRH agonist therapy the patterns of FSH and LH release suggested resumption of endogenous GnRH action on the pituitary with greater release of FSH than LH, a pattern that would be expected in the absence of ovarian steroid influence; 2) the lack of early estrogen production despite the increase in serum FSH concentrations suggests inadequate FSH secretion, abnormal ovarian responsiveness to FSH, or impaired FSH bioactivity; 3) androgen secretion was provoked by the increase in LH secretion; 4) per unit LH measured by bioassay, greater ovarian androgen secretion was stimulated in PCO than ovulatory women; and 5) the likelihood of spontaneous ovulation during recovery was minimal.

^* This work was supported in part by USPHS Research Grants AG-01512 and RR-865, and a grant from Ortho Pharmaceutical Corp.

Current address: Department of Obstetrics and Gynecology, College of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103.

Current address: Department of Obstetrics and Gynecology, Medical College of Virginia, Richmond, Virginia 23298.

To whom all correspondence and requests for reprints should be addressed.

^| Current address: Department of Obstetrics and Gynecology, University of California, Davis, Sacramento Medical Center, Sacramento, California 95816.

Received June 21, 1988.

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