The risks associated with hormone therapy may outweigh the benefits, according to new data from two hormone therapy trials within the Women’s Health Initiative. However, hormone therapy may still be justified for vasomotor symptom management among some menopausal women.
JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School, and colleagues reported on two WHI trials. The first was a 5.6-year intervention among women with an intact uterus who were randomly assigned to conjugated equine estrogens (CEE; 0.625 mg/daily) plus medroxyprogesterone acetate (MPA; 2.5 mg/daily; n=8,506) or placebo (n=8,102).
JoAnn E. Manson
The second looked at women who previously underwent a hysterectomy who were assigned to CEE alone (0.625 mg/daily; n=5,310) or placebo (n=5,429) for 7.2 years.
“Current WHI findings based on results from the intervention, postintervention and cumulative follow-up phases do not support the use of either CEE plus MPA or CEE alone for chronic disease prevention,” Manson and colleagues wrote. “Even though hormone therapy is a reasonable option for the management of moderate to severe menopausal symptoms among generally healthy women during early menopause, the risks associated with hormone therapy … preclude a recommendation in support of its use for disease prevention even among younger women.”
Estrogen plus medroxyprogesterone
In the first trial, 196 patients assigned to CEE plus MPA developed coronary heart disease (HR=1.18; 95% CI, 0.95-1.45) compared with placebo (n=159). Similarly, 206 patients in the CEE plus MPA group developed invasive breast cancer (HR=1.24; 95% CI, 1.01-1.53) compared with placebo (n=155).
Although other risk factors increased (ie, gallbladder disease, stroke, pulmonary embolism, dementia in women aged ≥65 years, and urinary incontinence), benefits included a decrease in hip fractures, diabetes and vasomotor symptoms, researchers wrote.
The risk for breast cancer continued during the 13-year cumulative follow-up period, with 434 patients diagnosed in the CEE plus MPA group vs. placebo (n=323; HR=1.28; 95% CI, 1.11-1.48), according to researchers.
“Overall, the risks of CEE plus MPA therapy during the intervention phase outweighed the benefits,” researchers wrote. “Most risks and benefits from CEE plus MPA dissipated postintervention.”
The risk–benefit ratio appeared balanced during the CEE alone intervention, with 204 cases of CHD compared with 222 cases in the placebo group (HR=0.94; 95% CI, 0.78-1.14), according to researchers.
Invasive breast cancer was diagnosed in 104 patients in the CEE alone group vs. 135 patients in the placebo group (HR=0.79; 95% CI, 0.61-1.02). Cumulative follow-up data indicated breast cancer diagnosis in 168 women in the estrogen group compared with 216 in the placebo group (HR=0.79; 95% CI, 0.65-0.97).
Stroke incidence increased during intervention and cumulative follow-up (HR=1.35 and 1.15, respectively), whereas hip fracture decreased by 33%.
“Among women with prior hysterectomy, the benefits and risks of CEE alone therapy during the intervention phase were more balanced,” researchers wrote.
Lessons from WHI
Overall, neither regimen significantly affected all-cause mortality. In the CEE alone group, patients aged 50 to 59 years tended to have more favorable results for all-cause mortality, myocardial infarction and the global index (P<.05), according to data.
Twelve adverse events occurred among patients aged 50 to 59 years per 10,000 women per year assigned to CEE plus MPA. Data also suggest that adverse events were more likely to occur in patients aged 70 to 79 years vs. patients aged 50 to 59 years.
In both treatment groups, researchers showed an increased risk for CHD among women aged 70 to 79 years with moderate to severe vasomotor symptoms at baseline (HR=5.79; 95% CI, 1.29-25.97 for CEE plus MPA, and HR=4.34; 95% CI, 1.43-13.14 for CEE alone). Women in the younger age groups showed no significantly higher risks.
“Overall, results for self-reported symptoms with both interventions were mixed and few additional quality-of-life benefits were observed,” researchers wrote.
In an accompanying editorial, Elizabeth G. Nabel, MD, of Brigham and Women’s Hospital and Harvard Medical School, said the WHI was thorough and objective in its clinical research.
“These findings demonstrate that menopausal hormone therapy has a complex profile of risks and benefits,” Nabel wrote. “The WHI has overturned medical dogma regarding the use of menopausal hormone therapy.”
For more information:
Manson JE. JAMA. 2013;310:1353-1368.
Nabel EG. JAMA. 2013;310:1349-1350.
Disclosure: The researchers report various financial ties with Amgen, AstraZeneca, MedStar Health, NIH, Novartis, Pfizer and UptoDate. See the study for a full list of individual disclosures.