Family Practice Grand Rounds Postmenopausal Osteoporosis and Estrogen Therapy: Who Should Be Treated? Lombardo F. Palma, MD Salt Lake City, Utah DR. LOMBARDO F. PALMA (Robert Wood It is estimated that 25 percent of white women Johnson Foundation Fellow, Department of Fam­ by the age of 65 years and 50 percent by the age of ily and Community Medicine): The objective of 75 years will have vertebral fractures, by far the Grand Rounds today is to discuss the cognitive most common complication in osteoporotic post­ process by which the family physician can make a menopausal women. Hip fractures have also been rational decision about estrogen therapy in post­ related to osteoporosis, and they are at least two menopausal women. I will briefly present some times more frequent in women than in men, de­ facts about osteoporosis, the physiology of meno­ pending on the age group.1 In the United States pause and subsequent bone demineralization, the there are about 200,000 hip fractures a year at an characteristics of women at risk of developing estimated cost of over one billion dollars, and 75 osteoporosis, and the therapeutic alternatives, as percent of those are probably due to osteoporosis. well as their risks and benefits. Then we will open Hip fractures are related to a high death rate in the the discussion. elderly (16 percent die within six months).1 This is a public health issue, as there are about four mil­ lion women in the United States who are sympto­ matic from osteoporotic fractures. From the Department of Family and Community Medicine, Menopause is the result of a sharp decline in the University of Utah Medical Center, Salt Lake City, Utah. At production of estrogens in women, a process the time this paper was written, Dr. Palma was a Robert Wood Johnson Foundation Fellow in the Department of which occurs in the United States at a median age Family and Community Medicine, University of Utah Medi­ of 50 years.2 This produces a sharp increase in two cal Center, Salt Lake City. Requests for reprints should be addressed to Dr. Lombardo F. Palma, Department of Family of the gonadotropin hormones, follicle stimulating and Community Medicine, University of Utah Medical Cen­ hormone and luteinizing hormone.2 ter, 50 North Medical Drive, 1C-303, Salt Lake City, UT 84132. The great majority of women will present some 0094-3509/82/020355-05$01.25 ® 1982 Appleton-Century-Crofts THE JOURNAL OF FAMILY PRACTICE, VOL. 14, NO. 2: 355-359, 1982 355 POSTMENOPAUSAL OSTEOPOROSIS symptoms of varying intensity and duration when In 1976, Lindsay et al conducted a study com­ going through the menopause. Some of these paring the mean metacarpal mineral content of 63 symptoms, such as vasomotor instability, may be women followed from three years after oophorec­ due to an unidentified factor in the hypothalamus.2 tomy and subdivided them into two groups; one Menopausal women may also present psychogenic group was treated with mestranol, and the other and metabolic problems. Examples of the latter received a placebo.5 During the five-year study the are demineralization of the bones, myalgia, skin bone mass of the treatment group did not de­ atrophy, senile vaginitis, and hyperlipidemia. Es­ crease, even increased slightly, while the placebo trogen affects four main target organs: the vagina, group showed a significant decrement in bone the uterus, the breast, and, our main subject to­ mass. This study has been continued, and a sec­ day, bone. ond report published, showing that four years after Osteoporosis is the result of an imbalance be­ mestranol was discontinued from 14 patients in the tween bone resorption and formation, resulting in treatment group, the bone mass of this new group net bone loss. The fundamental pathophysiology decreased to the level of 14 controls taking the of the various osteoporoses is still not resolved.3 placebo.8 It would therefore appear if estrogen The predisposition for osteoporosis in the elderly therapy for a postmenopausal patient were dis­ years has a sexual dimorphism.3 Women have continued, then four years later she would have greater, more precipitous, and earlier bone loss the same bone mass as a woman who has never than do men. Postmenopausal estrogen deficiency been treated. On the other hand, this study indi­ plays a significant role in women. There is also an cates that when estrogens are continued, they are ethnic polymorphism as a predisposing factor for effective in preventing bone loss for at least eight osteoporosis.3 The least pigmented races are more years. Although they studied oophorectomized pa­ vulnerable, and severe osteoporosis in blacks is tients, there is no evidence that such a group almost nonexistent. Total skeletal mass, physical differs from normal postmenopausal women. activity, nutrition, and genetic and cultural factors However, oophorectomized women are at higher also play a role in the development and progression risk of developing osteoporosis and secondary of osteoporosis.2 fractures because of decreased androgen and es­ In 1965, Meema et al compared the total bone trogen production. mass of women in their reproductive years to that The typical x-ray fdms of the dorsal lumbar of women after menopause.4 Their study shows spine of a white elderly woman with pathologic that women have a normal, constant bone mass osteoporosis show biconcavity and codfish type of throughout their reproductive years. However, vertebrae, swelling of the discs, and widening of postmenopausal women start losing bone mass at the intervertebral spaces. Additionally, there is a rate of 2.7 percent for the first few years and 0.7 marked decrement of calcification and loss of tra­ percent thereafter.5 In 1940, Albright, one of the beculae, and frequent compression fractures and early investigators of osteoporosis in postmeno­ wedging can be noted, by far the most common pausal women, in a paper published with co­ complications of postmenopausal osteoporosis.3 workers, coined the term “postmenopausal os­ Radiologic detection of osteoporosis is only pos­ teoporosis” to describe the pathological exacer­ sible after a 25 to 30 percent loss of the original bation of this physiologic event.6 In 1957, Henne- bone mass. The laboratory values of serum cal­ man and Wallach7 studied some postmenopausal cium, phosphate, alkaline phosphatase, and pro­ patients of Albright and plotted their height, dem­ tein electrophoresis are all within normal limits.3 onstrating how their height decreases between one As a consequence of fractures of the anterior to five inches in direct proportion to the number of body of the vertebrae, women lose height very years postmenopause without treatment. When suddenly and develop back pain. Fractures may be treated with estrogen, height loss was arrested in caused by walking around, lifting, walking up most cases. The authors also present another stairs, or even in the absence of significant physi­ group of nonosteoporotic postmenopausal women cal activity. Eventually, they develop kyphosis or who were being treated with estrogen for some “ dowager’s hump.” other reason, before and after the above group was Who are the women at high risk of developing treated. This group did not lose any height. osteoporosis? A number of conditions predispose 356 THE JOURNAL OF FAMILY PRACTICE, VOL. 14, NO. 2, 1982 POSTMENOPAUSAL OSTEOPOROSIS women to this malady, including the following: of Turns, for instance, contains 500 mg). 1. Women who have a small skeleton The most frequent estrogen therapy used in the throughout life have a higher tendency. United States is conjugated estrogens (Premarin) 2. The more frail the woman is, the higher the 0.625 mg per day cyclicly, 25 days out of a month chance she will develop osteoporosis. (prophylactic doses). There are some other estro­ 3. Women who have had an early oophorec­ gens on the market, but they all seem to have the tomy in life are more susceptible to this disease. side effects of uterine bleeding, breast engorge­ 4. Immobilization or sedentary lifestyle, as well ment or tenderness, weight gain, edema, nausea, as poor diet and decreased calcium intake and and heartburn. Mestranol 20 ^g, ethinyl estradiol malabsorption, can predispose one to osteoporosis. (Estinyl) 20 p,g and stilbestrol 0.5 mg are equiva­ 5. Women who have a small fat cell mass (lean lent to 0.625 mg of conjugated estrogens.3 body) are at greater risk. Postmenopausal women In the United Kingdom, the medical community produce androgens from their adrenal cortex and is surprised at how American physicians are treat­ ovaries. Androstenedione, specifically, is con­ ing postmenopausal women with estrogen alone. It verted into estrogen in the periphery by the blood, has been shown that progestins decrease the inci­ liver, and fat deposits.3 Therefore, the more fat dence of endometrial hyperplasia by producing cells a woman has, the more she will convert her endometrial shedding.10 With this therapy, women androgens into estrogens. Fat women may con­ with intact uteri continue to have cyclical bleed­ tinue to produce their own supply of estrogens ing. Some women feel very uncomfortable and do after menopause for up to 18 months. On the con­ not like this. Others are relieved that their symp­ trary, thin women will be at high risk of developing toms have been alleviated. Progestins are recom­ osteoporosis. mended for seven to ten days, in the latter part of 6. Hyperthyroidism, rheumatoid arthritis, and the cycle, along with estrogens.10 Good manage­ gastrectomy, as well as treatment with glucocorti­ ment of estrogen therapy (either alone or with pro­ coids, decrease the mineralization of bones. gestins) includes an annual endometrial biopsy, 7. Alcohol and tobacco consumption are other blood pressure check, and breast examination. factors that may increase the risk of developing Unusual bleeding or discharge also calls for diag­ osteoporosis.