Jurgen Sandow

Pituitary Gonadotropin Inhibition by a Highly Active Analog of Luteinizing Hormone-Releasing Hormone

Chronic treatment with highly active analogs of luteinizing hormone (LH)-releasing hormone (LH-RH) induces paradoxical antifertility effects. Intact male rats, a reduction in testosterone production is observed after the administration of [D-Ser(But)6]-LH-RH(1-9)ethylamide (burserelin, Hoe 766), 50 ng/day subcutaneously for 4 weeks. In castrated male rats treated with the same dose of analog, plasma LH levels were reduced from days 14 to 28 and plasma follicle-stimulating hormone (FSH) levels were reduced from days 21 to 28 of treatment. Pituitary LH and FSH concentrations were also decreased. The plasma prolactin level was reduced at 14 days of treatment. The hypothalamic LH-RH content remained unchanged and the adrenal corticosterone content was lowered. These findings indicate a direct inhibitory effect of the analog on gonadotropin secretion in the absence of the gonads, and may explain some paradoxical antifertility effects observed with high doses of LH-RH analogs which exceed the physiologic dose range.

Treatment of uterine fibroids with implants of gonadotropin-releasing hormone agonist: assessment by hysterography.

The effect of a potent, subcutaneously injected gonadotropin-releasing hormone (GnRH analog) (Buserelin, Hoechst, Frankfurt/Main West Germany) on the size of uterine leiomyomas and the uterine cavity area was studied in a group of 20 women. In all patients except 1, the uterine cavity area calculated by hysterosalpingography was decreased, with an average decrease of 35% (from 12.0 +/- 5.4 cm2 to 7.8 +/- 3.3 cm2) by 8 weeks of therapy. Significant decrease was observed in the group of women with initial uterine cavity area greater than 10 cm2. In patients with very large submucous fibroids, myomectomy by hysteroscopy and neodymium:YAG laser was easily performed. Rapid relief of symptoms such as menometrorrhagia permits the restoration of a normal hemoglobin concentration. In conclusion, use of GnRH analog represents an adjunct for preoperative reduction of tumor size and may permit surgical treatment by hysteroscopy.

Administration of nasal Buserelin as compared with subcutaneous Buserelin implant for endometriosis.

One hundred infertile patients with laparoscopically confirmed ovarian endometriosis were treated with either intranasal (IN) Buserelin (Hoechst, AG, Frankfurt am Main, West Germany) (300 micrograms three times a day) or subcutaneous (SC) Buserelin implant (6.6 mg Buserelin). Serum estradiol was suppressed in the menopausal range in both groups, but the inhibition of the pituitary ovarian axis appeared more profound and consistent in the SC group than in the IN group. Laparoscopic findings proved that the SC Buserelin emerged superior to the IN Buserelin. Indeed, the score of endometriotic lesions and the ovarian cyst diameter were more reduced in the SC group than in the IN group. Moreover, the histologic study showed a lower incidence of active endometriosis and a lower mitotic index of ovarian endometrial epithelium in the SC group than in the IN group. In conclusion, the release of a gonadotropin-releasing hormone agonist by a biodegradable implant achieved better efficacy in reducing endometriotic lesions than the IN mode of administration.

Long-term suppression of ovarian function by a luteinizing-hormone releasing hormone agonist implant in patients with endometriosis

Ten endometriosis patients received luteinizing hormone releasing hormone (LH-RH) agonist (buserelin) implant injections (6.6 mg subcutaneously) at days 0, 42, 84 and 126. Serum LH and follicle-stimulating hormone (FSH) were lowered by day 14. Luteinizing hormone remained at basal concentrations while FSH returned to values in the low-normal range of the menstrual cycle by day 35. At the end of the luteal phase during which treatment commenced, estrone and pregnanediol declined and remained at postmenopausal or early follicular phase values until days 305 to 460. Time to first ovulation ranged from 321 to 481 days after starting treatment. After the initial menstruation, only three instances of bleeding occurred during treatment. Pelvic pain was relieved or markedly reduced by day 42 and remained absent throughout the period of ovarian suppression. These results indicate the potential of a long-acting LH-RH agonist implant to form the basis for the treatment of symptomatic endometriosis.