Nacia Faure

Reversible hypogonadism induced by a luteinizing hormone-releasing hormone (LH-RH) agonist (Buserelin) as a new therapeutic approach for endometriosis

Ten women with endometriosis (stages I to IV) were treated with twice-daily subcutaneous injections of 200 micrograms of (D-Ser[TBU]6-des-Gly-NH2(10] luteinizing hormone-releasing hormone ethylamide (Buserelin) for 5 days followed by 400 micrograms intranasally three times daily for 25 to 31 weeks. Serum follicle-stimulating hormone levels returned to basal values on the second day of treatment, and serum luteinizing hormone levels progressively decreased to normal within 4 weeks. Serum estradiol decreased below early follicular phase levels within 7 to 30 days and continued to decrease to castrate levels. Light to moderate estrogen withdrawal bleeding was followed by amenorrhea with occasional bleeding or spotting in four women. Abdominal pain and dyspareunia disappeared or were ameliorated after 2 months of treatment. Resorption of endometrial implants was demonstrated by laparoscopy, and endometrial biopsy revealed atrophy or weak proliferation. Ovulation returned within 45 days, and two of four sexually active women became pregnant during cycles 3 and 5. The treatment was well accepted in spite of the expected hot flushes and vaginal dryness. Safety laboratory tests during and after treatment did not reveal any abnormalities. Reversible down-regulation of pituitary/ovarian function using repetitive luteinizing hormone-releasing hormone agonist administration can be a worthwhile approach to medical treatment of endometriosis.

Clinical efficacy and safety of low‐dose flutamide alone and combined with an oral contraceptive for the treatment of idiopathic hirsutism

BACKGROUND AND OBJECTIVE High doses of flutamide, which is the only antiandrogen that specifically blocks the androgen receptor, have recently been used with good clinical results in women with hirsutism. Since regression of hair growth requires long‐term therapy, clinical and economic considerations are important. The use of the lowest efficacious dosage could reduce costs. This study was undertaken to compare safety and efficacy of a low dose of flutamide (125 mg twice daily) alone and in combination with a triphasic oral contraceptive (OC) in women with idiopathic hirsutism.

Gonadotropins and estradiol responses to single intranasal or subcutaneous administration of a luteinizing hormone-releasing hormone agonist in the early follicular phase *

Single increasing intranasal and subcutaneous doses of a potent luteinizing hormone-releasing hormone (LH-RH) agonistic analog (D-Ser[TBU]6-des-Gly-NH2(10))LH-RH ethylamide (Buserelin) were administered on day 2 or 3 of the follicular phase in 59 normal women. Groups of five or six volunteers received intranasal doses ranging from 50 to 1300 micrograms and subcutaneous doses varying between 0.3 and 30 micrograms of the LH-RH agonist. Maximal amplitude of the serum gonadotropin response is observed at 6 hours. A sixfold increase is obtained for luteinizing hormone (LH) at a 200 micrograms intranasal dose, whereas maximal follicle-stimulating hormone (FSH) stimulation (threefold) is reached at a lower dose (100 micrograms). A 1000-micrograms dose elicits a more prolonged stimulation, levels of FSH and LH being two and five times above control levels at 11 hours. Similar response curves are obtained by the subcutaneous route, a maximal stimulation being reached at 3 micrograms for FSH and at 10 micrograms for LH. Serum estradiol levels are maximally increased at 11 hours after administration of 10 and 200 micrograms of the analog by the respective subcutaneous and intranasal routes. Twenty-four-hour response curves of gonadotropins indicate that the efficacy of the intranasal route is approximately 3% to 5% of the subcutaneous route. These observations should provide information useful in the investigation of the antifertility effects and medical treatments using an intranasal LH-RH agonist in the human being.

Ovarian sonographic findings during intermittent intranasal luteinizing hormone-releasing hormone agonist sequentially combined with an oral progestogen as antiovulatory contraceptive approach *

Ovarian ultrasounds were performed in four groups of six or seven women taking intranasal luteinizing hormone-releasing hormone agonist Buserelin (200 micrograms twice daily or 400 micrograms once daily) for periods of 14 or 21 days. Medroxyprogesterone acetate (5 mg by mouth twice daily) was added on days 15 to 21. A pause of 7 days followed each of the four treatment periods. Between days 12 to 15 of the first Buserelin cycle, sonograms showed in 17 cases (68%) various degrees of follicular stimulation ranging from numerous 4- to 10-mm follicles (24%), to 10- to 27-mm developing follicle(s) (24%), to greater than 27-mm ovarian cysts (20%). At the fourth Buserelin cycle, the predominant observation was large follicle(s) in the 14-day schedules, whereas ovarian scans did not reveal follicular stimulation in 66% of the 21-day schedules. The area under estradiol (E2) curves was above control in cycles with induced large follicles mainly in the 14-day schedules at the 200 micrograms/12 hour dose. Occasional brief and low elevation of progesterone was compatible with luteinized follicles. In the 21-day schedules at 400 micrograms/24 hours, absence of follicular development was frequently associated with serum E2 in the early follicular phase range. The most appropriate dosage regimen for potential contraception was 200 micrograms/12 hours for 21 days because it was associated with small follicles and serum E2 was in the range of control cycles.

ANTERIOR PITUITARY DOPAMINE RECEPTORS AND PROLACTIN SECRETION

ABSTRACT Dopamine (DA) receptors were characterized in the anterior pituitary (AP) of several species using H-labelled DA, dihydroergocryptine (DHE) and spiroperidol (SPIR). The majority of DA receptors in the rat AP were localized immunocytochemically on the plasma membrane of mammotrophs. Long term destruction of median eminence DA terminals resulted in a supersensitive-like response of AP DA receptors involved in the inhibition of prolactin. These data support DA as a prolactin inhibitory factor (PIF).

Endometrial histology during intermittent intranasal luteinizing hormone-releasing hormone (LH-RH) agonist sequentially combined with an oral progestogen as an antiovulatory contraceptive approach**Supported by the Contraceptive Branch of the National Institute of Health, contract 1-HD-0-2800.

Endometrial biopsies were performed in four groups of six or seven women treated for periods of 14 or 21 days with 200 micrograms twice daily or 400 micrograms once daily of intranasal Buserelin acetate. Five milligrams of medroxyprogesterone acetate (MPA) was taken orally twice daily on days 15 to 21. A medication-free week followed each treatment period. Between days 12 and 15 of the first treatment cycle, a proliferative endometrium was described in 16 out of 24 biopsies (66%). In 8 specimens (33%), early secretory changes were related to an early and/or short-lived rise in serum progesterone (P). At the end of the fourth treatment cycle, advanced maturation (days 23 to 28) was observed mainly in the 14-day schedules where serum estradiol (E2) was stimulated in or above the normal range of control cycles. Early to midluteal phase dating (days 16 to 22) was described mainly in the 21-day schedules. There was no P elevation in these groups. Five biopsies showing only proliferative tissue were associated with low levels of E2 mainly in the 400 micrograms/day group. The regimen capable of maintaining E2 in the low physiologic range (200 micrograms/12 hours X 21 days) was associated with incomplete secretory changes of the endometrium. A longer period of progestogen administration should produce a more complete maturation of the endometrium.