Estrogen, progestin combination decreases endometrial cancer risk in postmenopausal women

Continuous combined estrogen plus progestin use reduced the risk for endometrial cancer by 35% among postmenopausal women, according to an extended follow-up analysis of the Women’s Health Initiative trial.

Women assigned estrogen plus progestin also had a nonsignificant reduction in endometrial cancer deaths compared with women assigned placebo.

Rowan T. Chlebowski

“Continuous combined estrogen plus progestin use for 5.6 years in postmenopausal women with normal endometrial biopsy at therapy initiation resulted in a statistically significant reduction in endometrial cancer incidence, with the difference becoming statistically significant during longer-term post intervention follow-up,” Rowan T. Chlebowski, MD, PhD, chief of the division of medical oncology and hematology at Harbor–UCLA Medical Center, and colleagues wrote.

The Women’s Health Initiative initially enrolled 16,608 women aged 50 to 79 years with intact uteri with normal endometrial biopsy at entry. The researchers randomly assigned 8,506 women to once-daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate as a single pill. For comparison, 8,102 of the participants received matching placebo.

Researchers acquired consent for continued follow-up beyond the original trial from 12,788 (83%) of these patients (estrogen plus progestin, n = 6,545; placebo, n = 6,243).

After 5.6 years’ median intervention and 13 years’ median cumulative follow-up, endometrial cancer occurred less often in the women assigned combined hormone therapy than women assigned placebo (66 vs. 95; yearly incidence, 0.06% vs. 0.1%; HR = 0.65, 95% CI, 0.48-0.89).

Chlebowski and colleagues then evaluated these data based on endometrial cancer incidence during and after the intervention.

During the intervention, the difference in endometrial cancer incidence did not statically differ between the hormone therapy and placebo cohorts (25 vs. 30; HR = 0.77; 95% CI, 0.45-1.31). However, the difference in incidence of endometrial cancers that occurred postintervention reached statistical significance (41 vs. 65; HR = 0.59; 95% CI, 0.4-0.88).

A smaller proportion of women assigned the hormone therapy died of endometrial cancer; however, this difference did not reach statistical significance (5 vs. 11; HR = 0.42; 95% CI, 0.15-1.22).

The researchers acknowledged limitations of the study, including the small number of endometrial cancers that occurred and the lack of data on cancer treatment information.

Further, the researchers acknowledged the data only evaluated one hormone regimen.

“Consequently, the results cannot be extrapolated to other hormone regimens,” the researchers wrote.” “Whether regimens incorporating lower progestin dosage have similar endometrial cancer influence is unknown. While profound differences in pharmacology and in molecular actions between various progestins are described, clear differences in the clinic for endometrial cancer risk have only emerged for micronized progesterone use.” – by Ryan McDonald

Disclosure: Chlebowski reports speakers fees and honoraria from and advisory/consultant roles with Amgen, AstraZeneca, Novartis and Pfizer. The other researchers report no relevant financial disclosures.