Bruce B. Pharriss

Endometrial morphology in women exposed to uterine systems releasing progesterone

A blind study was done in 402 endometrial biopsies of women who had intrauterine devices releasing different daily amounts of progesterone or a placebo (empty device): 175 were obtained in what presumably was the proliferative phase and 227 in the secretory stage, as all these subjects were normal, healthy women with a history of previous fertility. With all dose levels of the progesterone-releasing devices there was variation of the endometrium general pattern and the over-all picture varied from normal secretory to suppressed endometrium. In addition to these changes of the endometrial pattern, in 231 specimens there was significant inflammatory infiltration and in six cases even plasma cells were seen. Predecidual reaction was frequently seen and in 45 cases it was diffuse and marked. The significance of these data is discussed on the grounds of the frequent similarities of the changes here reported with those in women using combined oral steroids for contraception.

Luteinizing hormone stimulation of ovarian prostaglandin biosynthesis.

Abstract Rat ovarian homogenates catalyse the synthesis of prostaglandin-like compounds from labeled arachidonic acid. When rats were injected with anti LH anti-serum this synthesis was suppressed. The suppression was overcome either by simultaneous LH injection or by addition of LH to the incubation media. This experiment is the first report of a tropic hormone sensitive prostaglandin synthesis system and provides evidence supporting a physiological role for prostaglandins in the ovary.

Uterine Therapeutic System for Long-term Contraception: II. Clinical Correlates

Some clinical correlates observed with use of the Progestasert uterine therapeutic system (UTS) are reported. The UTS is composed of a Tatum T intrauterine device which delivers either 20 35 or 65 mcg of progesterone daily. Of 617 women in the study about 1% of the total group became amenorrheic after insertion of the device and 19% experienced intermenstrual spotting. Breakthrough bleeding was the most common side-effect with the 20 mcg dose (5.5%). Menstrual cycle lengths were not affected. Endometrial patterns showed proliferative and secretorial phases that varied from the characteristic histologic patterns expected. Secretory phase histologies showed a slightly greater tendency towards a suppressed endometrium than did proliferative phase histologies which indicates increased progesterone activity. Vaginal cytology showed no changes during the proliferative phase. It is concluded from these early results that the UTS could be a highly effective and acceptable contraception method.

Values of steroidal intrauterine contraception for developing countries.

After a discussion of why IUDs did not pan out as the answer to fertility control in developing, nonindustrialized countries (basically medical problems with bleeding irregularities and perforations), the clinical experience with the progesterone-releasing IUD system (IPCS) in nonindustrialized countries is related. The medical advantages of a medicated or steroid-releasing IUD are obvious: high efficacy, postinsertion decreases in menstrual blood loss of about 40%, decreases in menstrual pain, low expulsion and perforation rates, and, in cases of accidental pregnancy, low spontaneous abortion rates. Also discussed is the apparent histological regression of the endometrium observed during progesterone-releasing IUD use in women with adenomatous hyperplasia. Lengthening the duration of efficacy to 5 years or more seems possible with progesterone, but achieving markedly longer duration will require a more potent synthetic progestagen.

Progestasert: A Uterine Therapeutic System for Long-term Contraception: I. Philosophy and Clinical Efficacy**Presented at the 29th Annual Meeting of The American Fertility Society, San Francisco, April 5 to 7, 1973.

An intrauterine steroid delivery system the Progestasert system, is described and studies of its clinical efficacy are reported. The Progestasert system combines the advantageous features of IUDs and oral minidose progestogen preparations. An internal device continuously delivers progesterone for 1 year to the uterine lumen and endometrium. A T-shaped Progestasert which releases 65 mcg/day has been selected for wide scale clinical use. A total of 3121 parous women used Progestasert systems for 25,389 woman-months. The pregnancy rate was 1%, the expulsion rate 2.8%, and the total removal rate was 13%. The total continuation rate of the Progestasert system of 83.2% compares favorable with that of the Tatum-T-shaped IUD of 68.7%. These initial results aft er 1 year of use are most encouraging and suggest that the goals originally set for a contraceptive approach using intrauterine progester one are well within reach.