CONCLUSIONS: In women with coronary disease, hormone therapy reduced the incidence of diabetes by 35%. This observation provides important insights into the metabolic effects of postmenopausal hormones but is insufficient to recommend the use of hormones for secondary prevention of heart disease.

20. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

JAMA. 2003 May 28;289(20):2651-62.

Comment in: Can Fam Physician. 2004 Feb;50:235-7. Evid Based Ment Health. 2003 Nov;6(4):111. JAMA. 2003 May 28;289(20):2717-9. JAMA. 2003 Oct 1;290(13):1706-7; author reply 1707-8. JAMA. 2003 Oct 1;290(13):1706; author reply 1707-8. JAMA. 2003 Oct 1;290(13):1707; author reply 1707-8. JAMA. 2003 Oct 1;290(13):1707; author reply 1707-8.

Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J; WHIMS Investigators. Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27104, USA. sshumake@wfubmc.edu

CONTEXT: Postmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy.

OBJECTIVE: To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo.

DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS.

INTERVENTION: Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303).

MAIN OUTCOME MEASURES: Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment. RESULTS: The mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia, 40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P =.01). This increased risk would result in an additional 23 cases of dementia per 10 000 women per year. Alzheimer disease was the most common classification of dementia in both study groups. Treatment effects on mild cognitive impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P =.72).

CONCLUSIONS: Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older. In addition, estrogen plus progestin therapy did not prevent mild cognitive impairment in these women. These findings, coupled with previously reported WHI data, support the conclusion that the risks of estrogen plus progestin outweigh the benefits.

21. Insulin resistance and weight gain in postmenopausal women of diverse ethnic groups.

Int J Obes Relat Metab Disord. 2004 Aug;28(8):1039-47.

Howard BV, Adams-Campbell L, Allen C, Black H, Passaro M, Rodabough RJ, Rodriguez BL, Safford M, Stevens VJ, Wagenknecht LE. 1MedStar Research Institute, Washington, DC, USA.

OBJECTIVE:: This study was conducted to examine the influence of insulin resistance on weight change in postmenopausal women of various ethnic groups.

SUBJECTS:: Data were obtained from 3389 women (60% White, 20% Black, 12% Hispanic, and 8% Asian/Pacific Islander), ages 50-79, enrolled in either the Women's Health Initiative Clinical trial or Observational Study, whose blood samples were selected randomly from the full cohort of 161 809 women for analyses.

MEASUREMENTS:: Glucose, insulin, and lipids were measured on fasting serum samples drawn at baseline and after 3 y of follow-up. Weight, height, waist circumference, and blood pressure were measured. Physical activity and energy intake were assessed via questionnaire. Insulin resistance was estimated using the HOMA (homeostasis model) calculation.

RESULTS:: Average age was 62 y, average BMI (body mass index) was 27.4 kg/m(2), and average weight change was a gain of 0.4 kg in 3 y. In a multivariate analysis, insulin resistance and insulin concentrations were independent predictors of increases in weight in White women (P=0.002 and 0.004, respectively) and in the combined group (P=0.027 and 0.039). For the whole group, after adjustment for other covariates, those in the highest quartile of insulin resistance gained 0.4 kg in 3 y, whereas those in the lowest quartile lost 0.06 kg. Similar trends were found for insulin resistance and weight gain in Hispanic and Asian/Pacific Islander women, but they did not reach statistical significance. In Black women, no relation was seen between either insulin or insulin resistance and weight change. A significant interaction between obesity and insulin resistance was observed (P=0.002 for White women and 0.032 for the whole group), so that there is weight gain with increasing insulin resistance in the leaner women, but weight loss with increasing insulin resistance in the most obese.

CONCLUSION:: Insulin resistance appears to be a predictor of weight gain in postmenopausal women, except for the most obese women. The effect is more pronounced in women who have a lower BMI, and the effect was not seen in the Black women who as a group had a higher BMI.International Journal of Obesity (2004) 28, 1039-1047. doi:10.1038/sj.ijo.0802645

22. Treatment of PCOS with metformin and other insulin-sensitizing agents.

Curr Diab Rep. 2004 Feb;4(1):69-75. Seli E, Duleba AJ. Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8063, USA. emre.seli@yale.edu

A significant proportion of women with polycystic ovary syndrome (PCOS) suffer from insulin resistance and compensatory hyperinsulinemia. Growing evidence indicates that elevated serum insulin induces hyperandrogenism, which in turn leads to anovulation and infertility. Hyperinsulinemia also contributes to the increased risk for cardiovascular disorders and type 2 diabetes mellitus. These concepts provide a rationale for therapies focused on treatments of insulin resistance.

Metformin is the most extensively studied insulin-sensitizing agent for the treatment of women with PCOS. Use of metformin leads to a decrease in serum insulin and androgen levels, as well as an improvement in ovulatory function.

Other insulin-sensitizing agents studied in women with PCOS include troglitazone, rosiglitazone, pioglitazone, and D-chiro-inositol.

23. Insulin-lowering agents in the management of polycystic ovary syndrome.

Endocr Rev. 2003 Oct;24(5):633-67.

De Leo V, la Marca A, Petraglia F. Department of Pediatrics, Obstetrics, and Reproductive Medicine, Institute of Obstetrics and Gynecology, University of Siena, 53100 Siena, Italy. deleo@unisi.it

Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple specialists together. Gynecologists, endocrinologists, cardiologists, pediatricians, and dermatologists are all concerned with PCOS patients and share research data and design clinical trials to learn more about the syndrome.

Insulin resistance is a common feature of PCOS and is more marked in obese women, suggesting that PCOS and obesity have a synergistic effect on the magnitude of the insulin disorder. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism, and metabolic disturbances. Women with PCOS should be evaluated for cardiovascular risk factors, such as lipid profile and blood pressure. Modification of diet and lifestyle should be suggested to those who are obese. Several insulin-lowering agents have been tested in the management of PCOS.