WHAT THIS EVIDENCE MEANS FOR PRACTICE
Early menopause puts our patients at elevated risk of osteoporosis, cardiovascular disease, neurodegenerative disease (possibly), and sexual dysfunction. We have long suspected that hysterectomy may accelerate the onset of menopause, and the North Carolina cohort study provides strong support for this hypothesis.
The New York State report reveals that ObGyns are more often practicing ovarian conservation in women (particularly younger women) undergoing hysterectomy for benign indications.
In 2008, ACOG revised its guidance on this matter—stating that “strong consideration should be given to retaining normal ovaries in premenopausal women who are not at increased genetic risk of ovarian cancer.”5 Evidence that we are increasingly following this prudent guideline is welcome news.
Breaking news: NAMS updates guidance on hormone therapy
Position Statement emphasizes differences in the benefit-risk profile of estrogen–only HT and estrogen-progestin HT
Periodically, NAMS assembles a multidisciplinary panel of clinicians and researchers to evaluate new evidence about HT and reach consensus on guidance about using hormones, and then publishes a Position Statement on the subject. In March, NAMS published its updated (2012) position on HT.
Two recent, and important, analyses of data from the Women’s Health Initiative (WHI)6,7 made an impact on the current revision to an earlier (2010) Position Statement; I had summarized those studies in the 2011 OBG Management Update on Menopause. One focused on breast cancer characteristics and mortality associated with use of combination estrogen-progestin HT; the other, outcomes after use of estrogen-only HT. Recap. Initial findings in the estrogen– progestin arm of the WHI, published in 2002,8 found that, after participants had used study medications (HT or placebo) for a mean of 5.2 years, their risk of invasive breast cancer was increased (HR, 1.26). This modestly elevated risk was only marginally significant (95% confidence limit, 1.00–1.59).
In 2010, investigators reported on breast cancer characteristics and mortality in WHI participants at a mean follow-up of 11 years. They found that combination HT users had breast cancer histology similar to that of subjects assigned to placebo, but that the tumors were more likely to be node-positive in combination HT users (23.7%, compared with 16.2% among placebo users). In addition, breast cancer mortality was slightly higher among users of HT (2.6 deaths, compared with 1.3 deaths, for every 10,000 woman-years of use) (HR, 1.96; 95% confidence interval [CI], 1.00–4.04); again, this elevated risk reached only marginal statistical significance.
Then, in 2011, WHI investigators reported their findings from the estrogen-alone arm of the study, in which post-menopausal, hysterectomized women were randomized to oral estrogen or placebo and took study medications for a mean of 6.8 years. (Recall that initial findings from the estrogen-only arm of WHI, published in 2004, found that the risk of invasive cancer was lower in women randomized to estrogen [HR, 0.77]—a reduction in risk that approached, but did not achieve, statistical significance [95% CI, 0.59–1.01].9) In the 2011 report, the lower risk of breast cancer in the estrogen group persisted; with almost 11 years mean follow-up, this prevention was found to be robust and statistically significant (HR, 0.77; 95% CI, 0.62–0.95).
The sobering increased risk of advanced-stage tumors and the marginally higher likelihood of fatal breast cancer associated with use of estrogen–progestin HT stands in stark contrast with the significant reduction in breast cancer associated with estrogen- only HT.
Dr. Kaunitz describes his approach to providing hormone therapy
Estrogen. Most of my patients who are taking systemic menopausal hormone therapy (HT) use transdermal estrogen, with 0.05 mg the most common starting dose. Given the elevated baseline risk of thrombosis among obese women, I particularly encourage them to use transdermal estrogen when starting systemic HT.
When I prescribe oral estrogen, the formulation I use most often is generic micronized estradiol; the most common starting dosage is a 1 mg tablet.
Progestin. To protect the endometrium in menopausal women whose uterus is intact and who are opting for systemic HT, I often use micronized progesterone, 100 mg nightly (provided no peanut allergy is present). My rationale? Progesterone is less likely than other progestational agents to cause unpleasant mood changes, and may offer a safety advantage vis a vis breast cancer.
When cost is a concern, generic medroxyprogesterone acetate tablets are well studied and inexpensive (2.5 mg tablets are appropriate when using the dosages of transdermal or oral estradiol given above).
When treating vasomotor symptoms/irregular bleeding in perimenopausal women, symptomatic relief may be more likely if HT formulations with sufficient progestin to consistently suppress ovulation are employed. Therefore, in such patients, I often use approaches such as femHRT 1/5 (also available as a generic) and Activella (also available as a generic).
Last, my experience is favorable using a combination of transdermal estrogen and the progestin-releasing IUD in symptomatic perimenopausal women.
Note: Using any sex steroids to manage perimenopausal symptoms constitutes an off-label use.