Book Review

Treatment of the Postmenopausal Woman: Basic and clinical aspects

N Engl J Med 2000; 342:1224-1225April 20, 2000

Article

Treatment of the Postmenopausal Woman: Basic and clinical aspects
Second edition. Edited by Rogerio A. Lobo. 704 pp., illustrated. Philadelphia, Lippincott Williams & Wilkins, 1999. $125. ISBN: 0-7817-1559-8

This scholarly book covers virtually all aspects of postmenopausal health. The discussions are clearly written, comprehensive, and concise, with basic aspects placed in a clinical context when possible. Often, a topic neglected in one chapter is addressed in a subsequent chapter. The numerous graphs have been thoughtfully chosen and are clearly presented, reflecting the essential points in the text. Students will appreciate the brevity of the discussions, with introductions that place the topics in context, and informed readers will benefit from the inclusion of the pertinent details of the most important studies. Most readers will not have to consult the original reports for additional information.

Everything is here: the complexity of premature ovarian failure, reproductive options during the perimenopause, the variability in the symptoms of the perimenopause, and the physiology and treatment of hot flashes. Thorough but brief chapters deal with vulvovaginitis; urinary tract disorders; collagen disorders of the skin, bone, and aortic wall; contraceptive use in older women; lipids; arterial changes; blood flow; vasomotor tone; carbohydrate metabolism; hemostasis; the pathophysiology of thrombosis; hypertension and contraceptive or noncontraceptive estrogens; compliance with therapy; and sexuality. One of the best chapters in terms of clinical layout addresses the evaluation and management of incontinence. The discussion is perfect for students. Phytoestrogens and herbs are discussed, including the growing evidence of the beneficial effects of the former and the limited evidence of the beneficial effects of the latter. The paucity of well-designed trials of androgens is apparent. The pharmacology of estrogens and progestogens is discussed, with long-overdue attention to the latter. Selective estrogen-receptor modulators are also discussed, but the most important studies showing reductions in the risks of spine fracture and breast cancer were reported after the publication of this book. Whether selective estrogen-receptor modulators accelerate or protect against degenerative disease of the central nervous system is unknown.

Large sections of the book discuss the epidemiology of cardiovascular disease, the epidemiology of sex hormone–dependent cancers, and cancer screening. The purported causative role of estrogen deficiency and curative role of estrogen replacement in disorders of the brain, especially Alzheimer's disease, cognitive dysfunction, and depression, are also discussed.

Although the discussions are balanced and critical, in my opinion they are not critical enough. Most beliefs about estrogen deficiency as a cause of cardiovascular or neurologic disease and about estrogen replacement as a means of prevention and cure are based on prospective and retrospective cohort studies and case–control studies, which are susceptible to a “healthy user” bias. Eliminating the bias requires a good study design, not statistics or meta-analyses. One well-designed randomized trial can, or should, make dozens of replicated (and therefore seemingly correct) observational studies crumble. Yet, the findings of the Heart and Estrogen/Progestin Replacement Study, reviewed only briefly in this book because of the timing of its publication, remain largely unaccepted or, at best, accepted with reservations. This is the first randomized, placebo-controlled trial that addresses the cardiovascular issue, and the results do not support the notion that hormone-replacement therapy reduces the risk of cardiovascular disease.

It is difficult to quantify mood, anxiety, and depression; to control for age-related events that occur pari passu with menopause; to extrapolate from observations in clinical studies to the community; and to rely on a retrospectively determined exposure to hormone-replacement therapy, which may be recalled differently by women who have had an infarct, stroke, cancer, or fracture than by controls. The scarcity of randomized, placebo-controlled trials and the poor scientific rigor of observational cohort or case–control studies should be loudly declared before inferences are made about estrogen deficiency as a cause of Alzheimer's disease. In my opinion, estrogen deficiency remains a cause in search of a disease of the mind or heart.

The discussion of osteoporosis in this book begins with a clear review of the epidemiology of fractures. The pathogenesis is discussed elegantly in the context of an imbalance between bone resorption and formation, which is the basis of bone loss. The descriptions of measurement methods, such as bone densitometry, are factually precise, but a clinically oriented presentation would have been helpful, with information on who should undergo measurements, with what machine and marker and how often; how the results should be used in decision making; and who should be treated, why, for how long, and with which drug. The chapter on bone markers is too negative. The chapter on the treatment of osteoporosis discusses hormone-replacement therapy in detail, but the bisphosphonates, the most rigorously investigated family of drugs in the field, are neglected. The recent reports on studies of the antifracture efficacy of raloxifene, residronate, and alendronate are not cited. A critical analysis of drugs such as calcitonin, etidronate, and vitamin D analogues would have been instructive, since these drugs are being used. Everything is in this book, but in some ways everything is everywhere, and further editing would have improved the cohesiveness of the text. Nevertheless, this is a reference book, there is an index, and my criticisms pale in comparison with the breadth and depth of the book, which I enjoyed reading and am delighted to recommend.

Ego Seeman, M.D.
University of Melbourne, Melbourne, Victoria 3084, Australia