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Estrogen Replacement Therapy for Postmenopausal Women With Diabetes

Karen E. Friday, MD

As a physician and a woman with diabetes, I tell my patients that the disease diabetes mellitus only chooses beautiful, talented, intelligent women. Although we are "chosen," we are also chosen to experience gender-specific complications if our disease management does not remain of prime importance for most of our lives.

The literature is mounting that normoglycemia will minimize or prevent many of the complications of diabetes, including blindness, renal disease, neuropathy, and peripheral vascular disease. However, being female does contribute an added risk for gender-related problems. The ages and stages of a diabetic woman's life bring increased risk at every milestone, despite exquisite attention to glucose control.

As children, there is concern for neurodevelopmental events. In these formative years, too-high or too-low glucose levels may affect both physical and cognitive development. For little girls with diabetes, puberty may be affected. Our tendency to increase insulin doses to compensate for the high concentrations of growth-related hormones may be overzealous, resulting in adolescent obesity, a problem with higher prevalence among girls, who tend to be more sedentary than boys. Then, as an adolescent girl attempts to lose weight, conflicts with meal planning, insulin adjustments, and caloric prescriptions enhance the risk of developing eating disorders.

In adulthood, there is initially an emphasis on reproductive issues. Pregnancy planning and attention to women's vascular health must be considered before pregnancy is undertaken.

As a woman with diabetes ages, her risk for cardiovascular disease increases. Again she is "chosen" to have this increased risk. Women without diabetes are protected, whereas women with diabetes "enjoy" equality with men in regard to risk for myocardial infarction or stroke.

An increase in adiposity with age continues to take its toll. Increased weight aggravates hyperinsulinemia and insulin resistance, which in turn increases the risk for hypertension, dyslipidemia, and atherosclerotic heart disease. Years of hyperinsulinemia also may stimulate androgen overproduction by ovarian theca cells, the outer lining of the ovary, and predispose to the development of polycystic ovarian disease.

At menopause, there are additional changes in insulin requirements, again causing more chaos at this life change than in women without diabetes. It is, therefore, not surprising that we have an increased risk for depression. Hormonal replacement programs can help stabilize the metabolic milieu and thus ease the transition into our mature years, while at the same time reducing the risk for heart disease and possibly stroke.

This Diabetes Spectrum FROM RESEARCH TO PRACTICE section validates the challenge for women to live healthy, happy lives despite having diabetes mellitus. The first article of this section (p. 180) opens our eyes to the overwhelming situation that adolescent girls encounter when they also have diabetes. Dr. Denise Charron-Prochownik and Dr. Silva Arslanian expertly teach us the intricate changes of pubescent diabetic girls. With this understanding, we can better design treatment options.

The next contribution is by Dr. Richard S. Legro and Dr. Andrea Dunaif (p. 185). These authors are experts in the association between insulin resistance and polycystic ovarian disease. Patients with these problems are at high risk for developing type 2 diabetes. Legro and Dunaif teach us that the ovary is a "victim" of the insulin-resistant state. A consequence of elevated insulinemia is a thickening of the outer theca layer of the ovaries, predisposing to cyst formation and resulting in infertility with ovulatory dysfunction. The thickened theca layer increases the production of testosterone, resulting in acne, excess body hair, and infertility. If the androgen excess is more severe, women may experience male-pattern balding, increased muscle mass, deepening of the voice, and increased libido. Although the last mentioned consequence may be considered a benefit, a myriad of adverse consequences of increased androgens can wreak havoc in a woman's life.

Legro and Dunaif also explain in detail the pathophysiology of polycystic ovarian disease and the relationship between the insulin resistance syndrome, which is observed in women with type 2 diabetes as well, and this pathological ovarian state. From the pioneering work of Legro and Dunaif's group, we learn a great deal about the causes and management of other insulin-resistant states and how these contribute to the risk for the development of diabetes.

Our third article, by Dr. Marsha Marcus and Ms. Michele Levine, is a thoughtful and careful review of eating disorders and their relevance to women with diabetes (p. 191). All women with diabetes need to pay particular attention to meal planning and carbohydrate type and distribution. Does this constant obsession with food predispose us to eating disorders? Do women with diabetes answer questionnaires in a way that wrongly labels us as having eating disorders, or do we actually have a disorder by definition?

When an eating disorder interferes with the ability to control diabetes, regardless of whether a verifiable diagnosis is made, clinicians must be able to make nutritional modifications and changes in medications to help women with diabetes with their interactions with food. Every woman with type 1 diabetes learns very quickly that it is easy to lose weight merely by omitting insulin. In fact, a glycosylated hemoglobin of >11% may be a pathognomonic sign that a young woman has an eating disorder, since even in the worst care settings, the mean glycosylated hemoglobin is usually not much higher than 9%. In fact, in the feasibility phase of the Diabetes Control and Complications Trial, two injections per day and urine checking for glycosuria in the standard care group resulted in a mean glycosylated hemoglobin of 9%. Only insulin omission produces a glycosylated hemoglobin >11%. These authors offer treatment strategies that are most appreciated for clinicians who must deal with young women whose diabetes is markedly out of control.

We next are treated to a wonderful "point-counterpoint" discussion of the cost-effectiveness of preconception counseling for women with diabetes (p. 195 and p. 201). Only 5,000 women with type 1 diabetes conceive each year in the United States. Given that, does it make economic sense to prescribe intensive management for the 160,000 women per year who have diabetes and are of child-bearing age? Wouldn't it be easier to wait until women become pregnant and offer intensive therapy only to those who may benefit most?

Dr. Donald Coustan and Dr. John Kitzmiller have both devoted their careers to the research and care of pregnant women with diabetes. Both would have naturally written an elegant article on the rationale for offering intensive preconception care for women with diabetes. I thought I would need to arm wrestle to convince one of these scientists to write the "con" side of this debate. To my surprise, both were intrigued about the prospect of emphasizing the need for preconception care by writing the contrary view. In the end, Don and Jack flipped a coin for the "honor" of writing the argument against preconception control. Thus, presented in this special section is a brilliant discussion of the pros and cons of offering preconception care programs for women with diabetes.

As a woman with diabetes ages, the hormones that increase the insulin requirement through their anti-insulin effect start to wane. Consequently, the insulin requirement can decrease, and a previously stable glucose level may now become unstable with bothersome insulin reactions. Insulin doses can be adjusted as a woman enters the perimenopausal state of hormonal fluctuations and eventually menopause.

Once menopause is established, hormone replacement therapy should be started if there are no contraindications. Prescriptions for postmenopausal hormone replacement therapy are best when hormonal levels are maintained in a stable range. Insulin doses can then be held constant without the need for frequent dose adjustments. Steady-state hormonal concentrations can be thought of as a benefit of finally outgrowing the rhythmic changes of the menstrual cycle, in which many women face monthly increases in the insulin requirement by as much as 20%. The new-found monotony of a steady dose of insulin is most welcome after 40 years of chaos. Dr. Karen Friday emphasizes the benefits of hormone replacement therapy for women with diabetes and suggests treatment options (p. 203).

Dr. Thomas Smitherman and Dr. Steven Reis, both cardiologists and experts in the care and management of cardiovascular disease, have written a comprehensive review focusing on the accentuated risk for heart disease in women with diabetes (p. 207). From this article, we learn that diabetes negates the protection from heart disease enjoyed by menstruating nondiabetic women, as the usual protective effect of being female is lost.

Although the article emphasizes this stark fact, it also offers strategies for minimizing women's risk for heart attacks and strokes. Yes, we must maintain glucose levels as near to normal as we can, but there is an even stronger rationale for strongly considering hormone replacement therapy as we reach menopause. Hormone replacement therapy can minimize by as much as 50% the additional risk for coronary artery disease contributed by menopause in both women with and without diabetes.

In addition, if we pay attention to a program of vigorous cardiovascular exercise, we can be rewarded with a long, healthy life. Such a program should focus on keeping the heart rate in the training range for 20 minutes at least 3 times a week, while maintaining weight through diet, paying attention to blood pressure control, and targeting HDL levels to >47 mg/dl. Smitherman and Reis motivate readers to encourage women with diabetes to improve their risk factors, and they place a special emphasis on cessation of smoking, since diabetic women who smoke are "adding fuel to the fire."

Last, but certainly not least, is an article by Ms. Linda Griffith and Dr. Patrick J. Lustman devoted to depression in women with diabetes (p. 216). Because self-care behaviors take so much effort, only when we behave ourselves and feel good can we ever continue the marathon of tasks needed to improve our lives. When depression strikes from any cause, be it situational or due to intrinsic factors, self-care behaviors suffer and are often forgotten. The result is a loss of glucose control.

Hyperglycemia can aggravate depression, and thus a vicious cycle ensues. It does not help for clinicians to add anger to the situation by reprimanding women to take better care of themselves. In the case of severe depression, hospitalization may be indicated to interrupt this vicious cycle. Antidepressant medications may be considered to improve mood and thus allow for better glucose control. This contribution on depression in women with diabetes is a thoughtful, caring, and helpful addition to the literature. It not only offers a nonjudgmental discussion of the destructive behavior that depression elicits, but also outlines constructive solutions to what previously seemed an impossible situation. As a woman with diabetes, I thank Ms. Griffith and Dr. Lustman personally.

Perhaps readers will finish these articles and conclude that the information provided simply reinforces intuitive notions regarding treatment at each life stage of a woman with diabetes. But then again, at least 50% of the clinicians who read these articles will learn from them how to be a better health-care provider for women with diabetes. This FROM RESEARCH TO PRACTICE section on diabetes in women is dedicated to the 50% of clinicians who are willing to learn more about us.

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Last updated: 9/23/97
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