Fernand Labrie
Molecular Endocrinolog, and Oncology Research Center, Laval University Medical Centre (CHUL), Quebec G I V 4G2, Canada.

Since breast and uterine cancers represent 1/3 of all cancers in women while cardiovascular disease and osteoporosis are the main causes of mortality and morbidity. the ideal compound at menopause would be the one having preventive as well as curative effects on all these diseases having a major impact on women's health. While Tamoxifen, the first SERM, has been demonstrated to have major beneflits at all stages of breast cancer, its partial estrogenic activity, especially its stimulatory effect on the endornetrium, limits its long-term use, especially as adjuvant therapy or in a preventive setting. Raloxifene, a 2nd generation SERM showing much reduced estrogenic activity. has already shown important benefits in reducing the incidence of breast cancer and bone fractures among a series of compounds which show various antiestrogenic/estrogenic activity ratios, EM‑652 (SCII 57068). a benzopyran derivative, is a SERM having pure andestrogenic activity in the. mammary gland and endometrium, while preventing bone loss and decreasing serum cholesterol and triglycerides in the rat. It also decreases far accumulation and decreases insulin resistance. Its activity against breast cancer has been demonstrated in women who had failed to Tainoxifen. There are good reasons to believe that the ideal hormone replacement therapy could well become a reality with a SERM in combination with an estrogenic and an androgenic component.

David T. Baird
Centre for Reproductive Biology, University of Edinburgh, Edinburgh

Progesterone controls most, if not all, of the key events which regulate reproductive function in female mammals. It is essential for the initiation, establishment and maintenance of pregnancy; and withdrawal of its secretion results in menstruation, parturition and/or lactation. The synthesis of the progesterone antagonist mifepristone (RU486) in 1980 by chemists at Roussel - UCLAF provided the means of developing a totally new approach to fertility control by blocking the "hormone of pregnancy". It was very rapidly demonstrated that antigestogens will induce bleeding in early pregnancy and mifepristone in combination with a prostaglandin is used as a method of inducing abortion in several countries. Mifepristone will also prevent follicle growth, rupture and ovulation as well as implantation and hence could be used as the basis for development of novel methods of contraception. These include 1) continuous daily pill which inhibits ovulation and menstruation; 2) a once-a-month pill which prevents implantation; 3) a "menstrual induction" pill which disrupts implantation; 4) an impregnated IUCD which induces amenorrhoea; 5) an emergency or post-coital contraceptive.
Surveys of women in Asia, Africa and Europe have provided evidence that many women would welcome these new methods to add to the limited range of contraceptives currently available. However the publicity surrounding the discovery of RU486 and protests by antiabortion organizations have inhibited research into the alternative uses of antigestogens. Paradoxically by offering the possibility of providing a wide range of effective contraceptives, the "the abortion pill" may reduce the number of unplanned pregnancies and hence the demand for abortion.

In 1956, my former head asked me to establish a reproductive endocrinology unit. As China is a developing country, we are short of diagnostic and therapeutic measures. Patients were mostly poor. We have to find simpler, inexpensive and yet effective ways to treat our patients. In a word, we must develop on our own. We start with BBT and vaginal smear as diagnostic measures and the only estrogen available was DES. The first problem we encounted was induction of ovulation in adolescent anovulatory uterine bleeding after bleeding controlled with progesterone withdrawal. We found a traditional Chinese medicine prescription that could induce ovulation and many patients got pregnant with this prescription. The next was improvement in dose reduction of oral contraceptives to 1/4 of the original dose, and extended further in clinical treatment such as HRT and is now widely accepted in reducing OCs and treatment dosages. Suppresion of ovarian function successfully with steroids in the management of precocious puberty. Innitiated a new classification for disorders of sexual differentiation, by grouping them into chromosome, gonad, and dysfunction of sex hormones and classify diseases according its cause. Finally, the Chinese philosophy in the management of menstrual disturbances by "rejustment of menstruation" influenced us in clinical management of menstrual disturbanees in just simply executing readjustment.