Individualizing hormone therapy to minimize risk: accurate assessment of risks and benefits.

Contrary to the exaggerated risks associated with HRT that developed after the initial press reports held by the Women's Health Initiative (WHI) writing group, the recent approach to hormone therapy is more balanced and evidence based. A review of over 40 years of scientific studies demonstrates that estrogen is a medication that can decrease mortality, cardiovascular disease, osteoporosis fracture, urogenital atrophy and dementia. When timing of administration, dose of therapy and route of administration are considered, estrogen is associated with low risks and substantial benefits. The decision of whether or not to take HRT for either short symptom relief or for long-term therapy, should be based on an accurate risk-benefit analysis. Adjusting the dose of therapy and considering a transdermal approach, particularly in high-risk patients, are important considerations.

Ovarian conservation at the time of hysterectomy for benign disease.

Approximately 78% of women between the ages of 45 and 64 years have prophylactic oophorectomy when hysterectomy is performed for benign disease to prevent the development of ovarian cancer. However, after menopause, the ovary continues to produce androstenedione and testosterone in significant amounts and these androgens are converted in fat, muscle, and skin into estrone. Evidence suggests that oophorectomy increases the subsequent risk of coronary heart disease (CHD) and osteoporosis and whereas 14,000 women die of ovarian cancer every year nearly 490,000 women die of heart disease and 48,000 women die within 1 year after hip fracture. PubMed and the Cochrane database were used to identify studies that examined the incidence of disease and mortality from 5 conditions that seem to be related to ovarian hormones: CHD, ovarian cancer, breast cancer, stroke and hip fracture, and also data for death from all other causes. The data were applied to a Markov decision analytic computer model to calculate risk estimates for mortality from these conditions until the age of 80. The model shows for a hypothetical cohort of 10,000 women undergoing hysterectomy and who chose oophorectomy (vs. ovarian conservation) between the ages of 50 and 54 [without estrogen therapy(ET)], that by the time they reach age 80, 47 fewer women will have died from ovarian cancer, but 838 more women will have died from CHD and 158 more will have died from hip fracture. Therefore, the decision to perform prophylactic oophorectomy should be approached with great caution for the majority of women who are at low risk of developing ovarian cancer.

Ovarian conservation at the time of hysterectomy for benign disease.

OBJECTIVE: Prophylactic oophorectomy is often recommended concurrent with hysterectomy for benign disease. The optimal age for this recommendation in women at average risk for ovarian cancer has not been determined. METHODS: Using published age-specific data for absolute and relative risk, both with and without oophorectomy, for ovarian cancer, coronary heart disease, hip fracture, breast cancer, and stroke, a Markov decision analysis model was used to estimate the optimal strategy for maximizing survival for women at average risk of ovarian cancer. For each 5-year age group from 40 to 80 years, 4 strategies were compared: ovarian conservation or oophorectomy, and use of estrogen therapy or nonuse. Outcomes, as proportion of women alive at age 80 years, were measured. Sensitivity analyses were performed, varying both relative and absolute risk estimates across the range of reported values. RESULTS: Ovarian conservation until age 65 benefits long-term survival for women undergoing hysterectomy for benign disease. Women with oophorectomy before age 55 have 8.58% excess mortality by age 80, and those with oophorectomy before age 59 have 3.92% excess mortality. There is sustained, but decreasing, benefit until the age of 75, when excess mortality for oophorectomy is less than 1%. These results were unchanged following multiple sensitivity analyses and were most sensitive to the risk of coronary heart disease. CONCLUSION: Ovarian conservation until at least age 65 benefits long-term survival for women at average risk of ovarian cancer when undergoing hysterectomy for benign disease.