Ovarian Suppression in Polycystic Ovarian Disease During 6 Month Administration of a Luteinizing Hormone‐releasing Hormone (Lh‐rh) Agonist

Abstract

This study was designed to evaluate the long-term effect (6 months) of the luteinizing hormone-releasing hormone (LH-RH) agonist buserelin on pituitary and ovarian function in a group of 14 patients presenting with the polycystic ovarian (PCO) syndrome. Buserelin was given subcutaneously 200 micrograms three times daily for the first 7 days followed by 500 micrograms once daily. Blood samples were taken weekly for the first month and then every month for radioimmunoassay of LH, FSH and sex steroids. While LH levels were stimulated during the first 2 weeks and then declined towards baseline, serum FSH levels were reduced after only 1 week (P less than 0.05). Serum oestradiol levels were maximally suppressed to the menopausal range after 1 month and testosterone levels were also significantly inhibited (P less than 0.05) after 2 weeks of therapy. Dehydroepiandrosterone (DHEA) sulphate did not show any significant change while 17-hydroxyprogesterone was suppressed after the first month of buserelin administration (P less than 0.01). The apparent divergent response of the gonadotrophins and the reduction of ovarian steroids in spite of lack of suppression of LH levels can be explained by the marked inhibition of the bioactivity of LH assessed by dispersed mouse Leydig cells assay. The clinical evaluation of hirsutism did not detect any change during the 6 month period. No patient had any menstrual bleeding or spotting after the sixth week of buserelin. The monthly incidence of hot flushes varied between 50 to 66%. This study shows that LH-RH agonist administration can selectively inhibit ovarian function and could be an interesting approach to evaluate the respective contribution of the ovary and adrenal on the pathophysiology of the polycystic ovarian disease. Polycystic ovarian (PCO) syndrome is characterized by tonic and exaggerated secretion of LH leading to an excessive stimulation of the ovarian stroma and an increased production of androgens (Yen et al., 1970; DeVane et al., 1975; Rebar et al., 1976). The androgen precursor delta 4 androstenedione is transformed in peripheral tissues into oestrone (Siiteri & MacDonald, 1973), thus maintaining the state of pituitary hypersensitivity and creating a positive feedback (Yen et al., 1976). The starting point of this vicious circle is still controversial; some argue for a hypothalamic abnormality (Vaitukaitis, 1983) while others support the peripheral origin of the hypersecretion of steroids (Reyniak, 1983). The importance of the adrenal contribution in this syndrome is still unclear.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Appreciation of LHRH Analogue Formulations

“…In an anovulatory woman, we have adminis tered a progestogen for a few days and then started the treatment during the phase of induced uterine bleeding. A similar initial stimulation of ovarian activity has then been observed [9].…”

Phasic serum lipid excursions occur during cyclical oral conjugated oestrogens but not during transdermal oestradiol sequentially combined with oral medroxyprogesterone acetate

“…LH and FSH antibodies were supplied by the NIH (National Institute of Health; Bethesda, Maryland, USA), and T antibody by Calbiochem (San Diego, California, USA) while rabbit anti-Ez were those currently available in our laboratory (Faure & Lemay, 1987). Human FSH-LH reference preparation, LER 907 (National Hormone and Pituitary Program, NPA, Baltimore, Ma.…”

Gonadotropin and Ovarian Steroid Production in Polycystic Ovarian Syndrome during Suppression with a Gonadotropin-Releasing Hormone Agonist

“…This last observation suggests that ovarian steroid produc tion in PCO can be influenced by suppressing endoge nous gonadotropin activity with GnRH agonists, and this has in fact been demonstrated [12][13][14][15]. However, previous studies with GnRH agonists have demon strated conflicting data on LH activity, since both a sig nificant decrease [13,14] as well as a marked increase [12,15] were reported. Faure and Lemay [15] demon strated an increase in immunogenic LH activity during 4 weeks of treatment with a GnRH agonist, while at the same time there was a definite decrease of bioactive LH activity.…”

“…There is thus increasing evidence that PCO is of primarily ovarian origin, however, influenced by an intact hypothalamic/hypophyseal feedback mechanism [8]. This last observation suggests that ovarian steroid produc tion in PCO can be influenced by suppressing endoge nous gonadotropin activity with GnRH agonists, and this has in fact been demonstrated [12][13][14][15]. However, previous studies with GnRH agonists have demon strated conflicting data on LH activity, since both a sig nificant decrease [13,14] as well as a marked increase [12,15] were reported.…”