Endometrial biopsy specimens were obtained from 12 healthy women under chronic intranasal luteinizing hormone-releasing hormone (LH-RH) agonist treatment for evaluation of the risk of endometrial hyperplasia during long-term inhibition of ovulation. A single daily dose of 400 or 600 microgram of the superactive LH-RH agonist D-Ser(TBU)6-EA10-LH-RH was given for 13 to 55 weeks. Treatment was monitored by clinical examination, basal body temperature (BBT) recordings, and frequently taken venous blood specimens for determination of estradiol and progesterone. Ovulation was inhibited during all but 2 of the 102 treatment cycles. No pregnancy occurred. Six of the women had slight menstrual-like bleeding, and six hac amenorrhea during the treatment period. No dysfunctional uterine bleeding occurred. The dominating histologic picture of the 17 endometrial biopsies, obtained after 78 to 380 days of treatment, was inactive or weak proliferative glands with slightly atrophic stroma. There were no signs of hyperplasia. After discontinuation of treatment ovulatory menstrual cycle rapidly returned.
PIP: The risk of endometrial hyperplasia during long-term inhibition of ovulation by luteinizing hormone-releasing hormone (LH-RH) agonist was investigated in 17 endometrial biopsy specimens from 12 22-36 year old women (mean age 29.6 years). The volunteers were treated for 13-55 weeks with a single daily 400 or 600 mcg dose of the the LH-RH agonist, D-Ser(TBU)6-EA10-LH-RH, administered intranasally. Endometrial biopsies were done after 78-380 days of treatment. Half of the women had amenorrhea and the other half had one or more episodes of uterine bleeding during treatment, but there was no dysfunctional bleeding. Biopsy specimens showed 6 inactive endometria and 9 weak proliferative endometria with slightly atrophic stoma. There were no signs of hyperplasia, glandular cysts, or atypia of the epithelium. Mean estradiol levels during treatment corresponded well with estradiol levels during the earlier follicular phases of the normal menstrual cycles. No pregnancies occurred. Ovulatory menstrual cycles rapidly returned after discontinuation of treatment; menstrual bleeding began an average of 45.3 days after treatment.