Intermittent GnRH antagonist plus progestin contraception conserving tonic ovarian estrogen secretion and reducing progestin exposure.
The present study was designed to evaluate the effectiveness of a once-weekly regimen of GnRH antagonist followed by a progestin as a potential new contraceptive method. On menstrual cycle days 2, 9, 16, and 23 (onset of menses = Day 1) monkeys were divided into two groups: 1) those injected sc with 0.1 mg/kg Nal-Glu GnRH antagonist in saline and those given only vehicle (control). On cycle days 15 to 26, each treated female was administered 25 micrograms norgestimate/day orally. This was continued for three treatment cycles (84 days). Weekly injections of Nal-Glu GnRH antagonist effectively blocked completion of folliculogenesis, ovulation, and corpus luteum function as judged by serum LH, E2, and P levels. Serum progesterone was undetectable (less than 0.1 ng/ml) during the treatment cycles. Importantly, serum estradiol levels during GnRH antagonist plus norgestimate treatments were maintained at 35 +/- 7 pg/ml. Upon the cessation of norgestimate treatment on day 26 in each cycle, menses uniformly began within 2 or 3 days. Regarding recovery, apparently normal and presumably ovulatory menstrual cycles, as judged by timely estradiol elevations, midcycle LH surges, and luteal phase progesterone patterns, were manifest immediately following termination of the final GnRH antagonist plus norgestimate treatment cycle. Endometrial biopsies removed on day 26 of control cycles, and on day 26 of the third treatment cycle revealed appropriate late secretory phase endometrium having tortuous endometrial glands and superficial stromal edema. Histological sections of ovaries removed at the end of the GnRH antagonist plus norgestimate treatment revealed multiple small and medium-sized developing and atretic follicles, having maintained serial ablation of the potentially maturing follicles.(ABSTRACT TRUNCATED AT 250 WORDS)
Danforth
D R
DR
Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk 23510.
Williams
R F
RF
Hsiu
J G
JG
Roh
S I
SI
Hahn
D
D
McGuire
J L
JL
Hodgen
G D
GD
D000818:Animals; D004359:Drug Therapy, Combination; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000494:pharmacology; D010053:Ovary / Q000166:cytology / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D011372:Progestins / Q000494:pharmacology*
D011372:Progestins; D007987:Gonadotropin-Releasing Hormone; D009644:Norgestrel; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C017576:norgestimate