A Contemporary Approach to the Menopause

David F. Archer, M.D.

This issue of Seminars in Reproductive Medicine is devoted to the use of hormone therapy in postmenopausal women. We have used the term postmenopausal women to describe women who have lack of ovarian function, naturally, surgically, or related to some medical condition such as breast cancer in which radiation and chemotherapy have resulted in ovarian failure. The postmenopausal female, whether she be natural and older as opposed to surgical or medical and younger, experiences a variety of physiologic alterations, probably the most important of which is the hot flash, considered the sine qua non of the menopausal female. Hot flashes, their attendant changes in sleep, their unpredictability, and/or their severity can have significant impact on quality of life in postmenopausal women. To understand the pathophysiology of the hot flash, we have asked Dr. Robert Freedman, who has extensively investigated changes in postmenopausal women in terms of the central nervous system control of the hot flash, to provide an article on the pathophysiologic mechanisms involved in the hot flash.

Also associated with the postmenopausal condition is the progressive loss of estrogen effect in the vagina and vulva. Although these changes may be construed as physiologic, they certainly can have a negative impact on the individual from the standpoint not only of symptoms but also of interference of sexual activity secondary to dyspareunia. Dr. Susan Ballagh provides us with an overview of the role of the vagina, not only as a functioning organ involved in coitus and secretion, but also as a route of administration of hormones for therapeutic intervention.

A second condition that is associated with advancing age and genetic risk factors is loss of bone resulting in osteoporosis in older women. Bone loss per se may not be significant, but the loss of integrity in the bone resulting in fractures, either spontaneous or with trauma, is clinically important. Dr. Michael Kleerekoper presents the relevant information on the use of estrogen in preventing bone loss.

Areas of controversy have entered the management of the postmenopausal female in the last 5 years. The role of hormone therapy and its effects on cardiovascular disease is one such area of controversy. Cardiovascular disease had been found to be reduced with estrogen, but this area is currently controversial. A persistent and consistent ongoing debate relates to the issue of breast cancer and hormones. Current studies, both observational and prospective randomized controlled trials, have again left us with a somewhat mixed result and without consistency in terms of the major questions, and these include the role of estrogen or estrogen plus progestin in heart disease and/or breast cancer. To address these issues, Dr. Janice Wagner and Dr. Thomas Clarkson present the animal models used to evaluate atherosclerosis and how they are applicable to the human. In addition, Dr. Vivian Lewis and Kathleen Hoeger address the nonhormonal approach to prevention of coronary heart disease. It is important, as Dr. William Creasman points out, that the direct correlation between hormones and breast cancer as a causative agent is lacking, although the association, albeit present, is relatively weak.

The aging population has brought with it its own current problems, particularly those that are related to the quality of life in the last few years before death. Nowhere is this more apparent than for the individuals who provide care for an older female suffering from cognitive loss. Whether or not hormones can indeed prevent significant loss of brain function and maintain cognitive ability in the older individual is an area fraught with uncertainty and yet one that deserves significant interest and research on the part of the practicing physician. Drs. JoAnn Pinkerton and Victor Henderson have brought together the current literature that would support, in a very indirect fashion, the role of estrogenic substances in preventing cognitive decline.

One should not forget that compassion, companionship, and caring often culminate in humans with intercourse or the act of coitus. Although sexuality, if defined as coital frequency, declines with aging in both men and women, sexuality probably still is the hallmark of what we construe as the interpersonal expression of caring between two adults. Female sexual decline is accepted as a norm, as is that associated with the male. The controversy today exists about whether or not hormones (estrogen or androgen, or a combination of both) are important in enhancing sexuality in an older woman. Dr. George Kovalevsky addresses this problem, describes the cycles, the interface of intimacy in the new paradigm, and presents us with the current evidence in favor of the use of estrogen and androgen for female human sexual behavior.

Because of the controversies, cardiovascular disease, breast cancer, and the clinical improvement associated with the use of estrogen on hot flashes, vaginal atrophy, prevention of bone loss, and the possible effects of estrogen on cognition and sexuality, the consumer and the practicing physician are faced with a current situation that is in flux. Whether we have been treating the postmenopausal woman with hormones inappropriately or in doses that are too high for her particular status are questions that remain unanswered at present. Because of the pressure on the physician brought by both regulatory and consumer issues, there has been a downward trend in the dosing of hormonal medication. It would be inappropriate to state that there is not a dose-response effect in terms of improvement of some symptoms, but there also is a dose-response effect in terms of side effects with medications. The higher dose is often associated with an attendant increase in adverse events. This has resulted in lowering the dose of both the estrogen and progestin. The expected outcome is to deliver a product that provides relief of the common menopausal symptomatology, hot flashes, vulvovaginal atrophy, and prevents bone loss while reducing side effects. Dr. David Archer reviews the use of the lower doses of estrogen plus progestin and their efficacy for hot flashes, vulvovaginal atrophy, bone, and lipids as a means of demonstrating that lower doses can be as efficacious and can offer the potential benefit of reducing side effects for the consumer.

This issue of Seminars in Reproduction addresses the postmenopausal woman, a group whose numbers are growing rapidly within the United States and the world, and whose medical problems increase with age. The fountain of youth has not been found, but the use of hormone therapy still appears to have a significant role for the relief of menopausal symptoms and the prevention of bone loss. Whether these changes and other physiologic effects of estrogen will be found to retard age-related diseases will be determined in the future.