Postgraduate Medicine

ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20

The pros and cons of estrogen therapy Albert Segaloff To cite this article: Albert Segaloff (1979) The pros and cons of estrogen therapy, Postgraduate Medicine, 65:6, 106-112, DOI: 10.1080/00325481.1979.11715176 To link to this article: http://dx.doi.org/10.1080/00325481.1979.11715176

Published online: 07 Jul 2016.

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Date: 17 August 2017, At: 09:41

Interstate Postgraduate Medical Assembly

The pros and cons of estrogen therapy

Albert Segaloff, MD

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Consider In addition to hormone deficiency, what are some indications for estrogen therapy? What concomitants ofaging can estrogen therapy prevent? Why is estrogen therapy not appropriate for women with irregular menses or galactorrhea?

Hormone deficiency is the most obvious indication for its use, but estrogen therapy is sometimes beneficial in other conditions. Since rather serious complications are now being associated with such therapy, however, a decision to use estrogen calls for caution in determining the dose and the duration of administration. Estrogen therapy is not the fabled fountain of youth. It does not slow the aging process (physicians, beauticians, dietitians, and physical therapists notwithstanding), nor does it prevent skin changes, sagging jowls, hypertension, psychologic difficulties, myocardial infarction, or ingrown toenails. The only concomitants of aging that it can prevent are atrophic vaginitis and the decrease in height associated with postmenopausal osteoporosis. The possibility of serious complications precludes extended use or high-dose therapy. Indications Hormone deficiency-Hormone replacement is the most obvious role for estrogen therapy. An effort should be made to administer the drug in physiologic fashion, ie, cyclically, so that therapy mimics the ebb and flow of normal estrogen production. The dose should be the smallest that will produce the desired effect, and attempts should be made periodically to discontinue therapy. Absence of ovaries-Estrogen therapy should be considered for girls and young women born without ovaries or in whom the ovaries have been destroyed or removed owing to accident or disease. The de-

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sired outcome of therapy is maturation of the skeleton; development of secondary sex characteristics, particularly the breasts; and if the uterus is present, establishment of menstrual bleeding. The dose and form of estrogen should be chosen to fit the patient's needs. For patients who cannot take oral medication or who are noncompliant, a monthly injection of estradiol valerate often provides the desired cyclic effect. The specter of possible malignant disease accompanies development of the breasts and maturation of the uterus. No compelling evidence currently indicates that patients receiving estrogen for hormone deficiency have an unusually high incidence of breast cancer. However, in a subset ofthese patients, ie, those with the ovarian agenesis of Turner's syndrome, the incidence of cancer of the endometrium is much higher than average. The cause is not clear. Such patients and their families should be warned carefully about the possible carcinogenic effect of hormone administration. Menopause-The gradual failure of estrogen secretion by the ovaries during menopause is a natural event through which most women sail with little or no difficulty. Some continued

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Illustration: Eric Fowler

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Before topical estrogen is prescribed for atrophic vaginitis, another type of lubricant should be tried. Topical administration of estrogen carries the same hazards as does systemic administration.

Diethylstilbestrol. Needlework representation by Dr and Mrs Albert Segaloff.

women have symptoms so minor that estrogen therapy is not indicated, but a substantial number commonly experience severe symptoms, such as debilitating vasomotor instability (resulting in hot flashes), severe arthralgia, and severe formication. Administration of large doses of estrogen for long periods is not the answer, however, for inevitably the hormone must be withdrawn, and the larger the dose and the longer the duration of therapy, the more difficult will be the withdrawal period. Therefore, estrogen administration always should be cyclic, the dose small enough so that symptoms are tolerable but not completely relieved, and therapy stopped as soon as possible. Many postmenopausal symp-

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toms are due to atrophic vaginitis, a condition that usually responds to topical application of low doses of estrogen. However, vaginal lubrication with a substance other than estrogen should be tried first; the atrophic vagina readily absorbs estrogen, and therefore topical administration carries the same hazards and drawbacks as does systemic administration. Again, the smallest feasible dose should be used for the shortest possible period. One of the most painful sequelae of the menopause is osteoporosis with subsequent collapse of vertebral bodies. The many seemingly careful studies of the effect of estrogen on calcium metabolism, bone density, and activity of osteoblasts and osteoclasts have produced a confusing array of opinions, fre-

quently diametrically opposed. The one thing about osteoporosis that does seem to have been proven is that cyclic administration of modest amounts of estrogen can prevent the decrease in height caused by this condition. It is this decrease in height and the pain from vertebral collapse that bother patients, not the density of their bones or the state of their calcium balance. Metastatic breast cancer-Estrogen is very effective in the treatment of metastatic breast cancer when 8S estrogen receptors (ERs) are present in the cytoplasm of the cancer cells. In such cases, administration of the hormone in appropriate dose and manner can lead to long-lasting, objective regression of metastatic disease. A small percentage of tumors that lack ERs also respond to estrogen, and therapy is thus worth a trial, even though the prognosis is less optimistic. When determination of the presence of ERs is not possible, knowledge of the distribution pattern of ER-positive tumors is helpful. A minority of premenopausal patients have such tumors, while the number of postmenopausal patients with ER-positive tumors increases with time after menopause. Therefore, the longer after menopause the tumor appears, the more likely it is to be ER-positive and to respond to hormonal manipulation. If bone is the primary site of metastasis, an androgen is a better

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Estrogen therapy is very effective in metastatic breast cancer when estrogen receptors are present in the cancer cells.

first choice for therapy than is an estrogen. Cancer ofprostate-The other type of cancer that responds to estrogen is cancer of the prostate. The optimal dose is still a matter for conjecture. Some doses cause substantial sodium retention, and in the elderly men in whom prostate cancer commonly occurs, sodium retention can lead to death from congestive heart failure. Patients must be watched carefully for this complication. Hemorrhage-lntravenous administration of water-soluble estrogen derivatives has been effective in stopping excessive bleeding of unknown origin. Estrogen is a hemostatic specific for uterine hemorrhage, and its use may save women from having to undergo a D and C or a more extensive operation.

Postpartum breast engorgement! believe, in common with the majority I hope, that nursing a newborn child is better for both mother and baby; however, for women who choose not to nurse their babies, estrogen is useful to prevent painful swelling of the breasts. The Federal Register of October 24, 1978, reports that there are efforts by the Food and Drug Administration to remove this indication from the estrogen package insert. To disallow this modest amount of estrogen after nine months of constant high endogenous estrogen levels seems another instance of misplaced overregulation.

Albert Segaloff Dr Segaloff is director of endocrine research. Alton Ochsner Medical Foundation, New Orleans. His research and teaching extend from organic synthesis through biologic and pharmacologic studies and clinical trials of synthesized materials.

Possible complications Cancer of endometrium- Within the limits of modern epidemiology, a higher-than-normal incidence of endometrial cancer appears to be a well-demonstrated complication of estrogen therapy in women at risk. The association seems to be both dose- and time-related, ie, the incidence of endometrial cancer is highest in women taking the highest doses of estrogen for the longest period.

Cardiovascular conditions-

There is increasing evidence that use of estrogen alone or in combination with other hormones in contraceptive pills can lead to increased blood pressure in susceptible women. This complication is, in general, reversible on cessation of therapy. Evidence also is growing that estrogen use leads to an increase in thromboembolic phenomena in young women taking the pill·and in postmenopausal women taking estrogen alone. Contrary to the old notion that estrogen protects

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Estrogen therapy is effective in cancer of the prostate, although the sodium retention it causes can lead to congestive heart failure in the elderly.

against myocardial infarction, recent evidence indicates that its use may increase the incidence of heart disease in elderly men with carcinoma of the prostate and in postmenopausal women.

Carbohydrate intoleranceSome evidence indicates that a decrease in carbohydrate tolerance is associated with estrogen use in some patients. This phenomenon also seems to be reversible when therapy is stopped. Breast cancer-Estrogen therapy may increase the risk of breast cancer in women. However, in Western urban society the baseline incidence of breast cancer is so high that statistical demonstration of an increase due to estrogen administration is difficult. Cancer of the breast does occur with increased frequency in transsexuals receiving large doses of estrogen and possibly in some men treated with estrogen for cancer of the prostate. In some of the latter cases the cancers contain acid phosphatase and are metastatic from the primary prostatic tumor. Pituitary adenomas-In laboratory rodents, prolonged continuous estrogen administration leads to development of chromophobe adenomas of the pituitary gland. These adenomas secrete prolactin. A high incidence of microadenomas of the pituitary and elevated serum levels of prolactin are found in women with irregular or absent menses or galactorrhea. Estrogen is commonly used to treat these conditions. At present

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it appears that such therapy may accelerate the growth and secretory rates of preexisting pituitary microadenomas, a circumstance that would contraindicate estrogen therapy in amenorrhea, irregular menstruation, or galactorrhea without careful monitoring of prolactin levels at least. Conclusion Estrogen therapy is not a panacea for aging but is indicated for certain conditions, such as hormone deficiency (most commonly severe menopausal vasomotor instability), metastatic breast cancer, and cancer of the prostate. When a decision to give estrogens is made, the pros and cons should be discussed candidly. Patients should be made aware that many of the "complications" are rare events and indeed that some are not even unequivocally proven. However, evidence is growing that possible complications of long-

term estrogen use may include hypertension, endometrial cancer, breast cancer, thromboembolism, and pituitary adenoma. Thus, the dose should be only large enough to produce the desired effect and therapy should be stopped as soon as possible. Presented before the 62nd annual scientific Assembly of the Interstate Postgraduate Medical Association. held in Hollywood. Florida. Address reprint requests to Albert Segaloff. MD. Alton Ochsner Medical Foundation, 1516Jefferson Hwy, New Orleans, LA 70121. Bibliography A MA Department of Drugs: Estrogens. progestogens, oral contraceptives, and ovulatory agents. In: AMA Drug Evaluations. Ed 3. Littleton, Mass. Publishing Sciences Group Inc. 1977, pp 540-572 Editorial: Estrogen therapy and endometrial cancer. Br Med J 1:209-210, 1977 Gray LA et al: Estrogens and endometrial carcinoma. Obstet Gynecol49:385-389, 1977 Lipsett MB: Estrogen use and cancer risk. JAMA 237:1112-1115, 1977 Records JW: Estrogens and cancer of the endometrium. (Editorial) South Med J 70:1-3, 1977

VOL 65/NO 6/JUNE 1979/POSTGRADUATE MEDICINE

The pros and cons of estrogen therapy.

Postgraduate Medicine ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20 The pros and cons of estrog...
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