New approaches to contraception.

Abstract

18 experimental contraceptives (13 for women 5 for men) which have progressed to the level of actual clinical trial are described. A biodegradable androgen implant lasting 1 year or longer (supplemented by a weekly pill or semiannual injection) has been found to suppress male sperm production while maintaining normal levels of plasma testosterone and is readily reversible. Trials of testoterone propionate testosterone enanthate and medroxyprogesterone acetate successfully suppressed spermatogenesis but potential complications include libido loss or gynecomastia when progestins are used and medical concern over metabolic disorders or cardiovascular hazards when potent androgens are used. Several removable clips which can be attached to the vas deferens through a small scrotal incision and 2 versions of a device (plug and a microvalve) which can be placed within the vas are under study but a satisfactory design has deferens through a small scrotal in with devices which cause sperm necrosis or immotility include: 1) surgical silk suspended within the lumen of the vas and fixed lossely to the perivasal surface to permit subsequent removal; 2) copper or zinc filaments which immobilize sperm or cause head-tail separation. The concept of partial sperm damage is attended by difficult issues of teratology. Heading the list for women are 2 progestin compounds medroxyprogesterone acetate and norethindrone enanthate which have been marketed in some countries as trimonthly contraceptive injections. Ovulation is prevented by suppression of the luteinizing hormone release but the safety and reversibility of the compounds has yet to be proven. The first biodegradable implants for women have been developed and may be clinically tested before the end of 1974. Evidence that ovulation can be suppressed by the absorption of progestins through the vaginal mucosa has led to the creation of 3 compounds incorporated into Silastic intravaginal rings. Similar to the shape and size of a diaphragm rim the rings can be inserted by the wearer and left in place for 1 month or longer. Steroid absorption through the skin has also been established and preliminary tests are being performed on Silastic arm braclets; contraceptive feasibility requires a design which provides a constant rate of absorption. The development of a monthly pill or suppository which induces menstruation could erradicate the risks of long term hormonal contraception but an effective compound has yet to be determined. Trials are in progress with at least 7 new types of IUD including 1 which is designed to remain within the cervix and others which release an antifertility agent into the uterine lumen. Copper carrying devices are the most advanced in testing and should be available in the near future. Ovulation supression tests with a compound of quinestrol and quingestanol have proven unsatisfactory. Identification and synthesis of the luteinizing hormone-releasing factor (LRF) has led to the potential use of this polypeptide for regulating ovulation in normally cycling women; a precisely timed ovulation could improve the effectiveness of the rhythm method. Although diethylstilbestrol is now available to minimize the risk of pregnancy following isolated midcycle exposure the side effects and disruption of the ovarian cycle render the compound unacceptable for regular postcoital contraception.