Many steroid hormones have a powerful impact on the dynamics of fat and glucose metabolism in the body. The actions of these hormones on metabolism, however, are often sex-specific. This is particularly true of "male" sex hormones (called androgens) such as testosterone and DHEA. These androgens are essential for the health of both men and women. But while higher testosterone levels generally cause men to burn up more fat and synthesize more lean muscle mass, in women, they may produce the opposite effect.1

Women with "androgen dominance" have bodies that produce excess levels of "male" hormones such as DHEA and testosterone. This hormonal profile in women is associated with an increased risk of many metabolic disorders.

High levels of testosterone and DHEA in women appear to promote central obesity - the tendency for excess fat deposits to accumulate around the waist.1,2 Women with this "apple-shaped" form of obesity have a much higher risk of developing type-2 diabetes, heart disease and polycystic ovary syndrome. In fact, in women with chronic androgen dominance, these disorders often develop simultaneously. Left untreated, sex hormone dysregulation and dysglycemia may perpetuate a vicious cycle of imbalances and poor health.

A key feature of type-2 diabetes is insulin resistance. This state develops as the body becomes increasingly insensitive to the effects of insulin. Attempting to compensate for insulin's reduced affect on target tissues, the pancreas pumps out even more of this hormone. This can result in chronically high circulating levels of insulin which, in turn, may cause specialized cells in the adrenal glands, called theca cells, to switch on (upregulate) an enzyme called 17,20-lyase.

17,20-lyase shifts the body's hormone production away from estrogens, toward the androgens (both androgens and estrogens are synthesized from the same source material), further promoting the dynamics of central obesity and insulin resistance.

Women with type-2 diabetes are also likely to have lower levels of sex-hormone-binding-globulin (SHBG), a protein that latches on to sex hormones and renders them biologically inactive.3 This deficiency may spur higher circulating levels of biologically active sex hormones, such as testosterone, that can promote metabolic mechanisms of obesity and insulin resistance in women.4

Unfortunately, the negative clinical effects of chronic sex hormone imbalances can extend far beyond dysglycemia and type-2 diabetes. For example, both high insulin levels and high levels of estrogen and androgens in women have been linked to increased risk of breast cancer.5-10 At elevated levels, these hormones are believed to provide stimulatory "fuel" for cell division, resulting in a cell proliferation process that may promote DNA damage and the growth of hormone-dependent tumors.

While guarding against excess is important, it's also crucial to prevent estrogen deficiency - especially in women with type 2 diabetes - to reduce the risk of related complications such as dementia and cardiovascular disease.

Several functional assessments can help the practitioner establish optimal sex hormone balance in women.

References:
1 Tchernof A, Labrie F, Belanger A, Despres JP. Obesity and metabolic complications:contribution of dehydroepiandrosterone and other steroid hormones. J Endocrinol 1996;150(Suppl):S155-64.

2 Mantzoros CS, Georgiadis EI, Evangelopoulou K, Katsilambros N. Dehydroepiandrosterone sulfate and testosterone are independently associated with body fat distribution in premenopausal women. Epidemiology 1996;7(50:513-5.

3 Defay R, Papoz L, Barny S, Bonnot-Lours S, Caces E, Simon D. Hormonal status and NIDDM in the European and Melanesia populations of New Caledonia: A case-control study. The Caledonia Diabetes Mellitus (CALDIA) Study Group. Int J Obes Relat Metab Disord 1998;22(9):927-34.

4 Haffner SM. Sex hormones, obesity, fat distribution, type 2 diabetes and insulin resistance: epidemiological and clinica l correlation. Int J Obes Relat Metab Disord 2000;24 Suppl 2:S56-8.

5 Stoll BA. Western nutrition and the insulin resistance syndrome: a link to breast cancer. Eur J Clin Nutr 1999;53(2):83-87.

6 Bruning PF, Bonfrer JM, van Noord PA, Hart AA, de Jong-Bakker M, Nooijen WJ. Insulin resistance and breast cancer risk. Int J Cancer 1992;52(4):511-6.

7 Cauley J, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR. Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Ann Int Med 1999;130:270-277.

8 Dorgan JF, Longcope C, Stephenson HE, Jr. Falk RT, Miller R, Franz C, Kahle L, Campbell WS, Tangrea JA, Schatzkin A. Serum sex hormone levels are related to breast cancer risk in postmenopausal women. Environ Health Perspect 1997;105(3):583-585.

9 Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, Banerjee S, Koenig KL, Shore RE, Strax P, Pasternack BS. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst 1995;87(3):190-197.