Estrogen and interrupted progestin: a new concept for menopausal hormone replacement therapy.

OBJECTIVE

We tested a new hormone replacement formulation based on the hypothesis that interrupted administration of progestin in the presence of continuous estrogen would result in receptor up-regulation and resensitization of target tissues to both estrogen and progestin. As a result, symptom control might be possible with lower doses of steroids and in the absence of withdrawal bleeding.

STUDY DESIGN

Forty postmenopausal women were entered in a 6-month pilot study, including an 18-month extension. They received piperazine estrone sulfate 0.75 mg daily. Norethindrone 0.35 mg daily was added in 3-day phases, alternating with progestin-free phases of 3 days. There was no steroid-free withdrawal period. We examined symptom control, bleeding patterns, endometrial protection, and lipid profiles in the women over the 24 months of the study.

RESULTS

Hot flushes were completely eliminated in 76% of women, and 80% had no bleeding by 6 months. There were three dropouts. Thirty-three women elected to continue after the first 6 months and completed 24 months on therapy for a compliance rate of 82.5%. No endometrial hyperplasia was seen on serial biopsies, and no changes occurred in lipids except for a small but statistically significant decrease in high-density lipoproteins and triglycerides at 24 months.

CONCLUSION

Our preliminary results of low bleeding rates, good symptom control, and endometrial protection suggest that hormone replacement with low-dose estrogen and interrupted progestin is effective and may lead to improved compliance in menopausal women.