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Updated: Aug 13, 2026

Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration
Published on: June 7, 2012
Low-dosage esterified estrogens opposed by progestin at 6-month intervals
B Ettinger1, A Pressman, A Van Gessel
1Division of Research, Kaiser Permanente Medical Care Program, Oakland, California 94611-5463, USA. bxe@dor.kaiser.org
Objective:
To estimate incidence of endometrial hyperplasia, vaginal bleeding, and menopausal symptoms in women who changed from standard monthly cyclic hormone replacement therapy (HRT) to half-strength estrogen opposed by medroxyprogesterone acetate (MPA) at 6-month intervals.
Methods:
We identified 138 women aged 55-75 years who had regularly used HRT at a standard dosage (equivalent to 0.625 mg conjugated estrogen) opposed by cyclic monthly MPA. Each subject's HRT regimen was changed to 0.3 mg/day esterified estrogens (Estratab; Solvay Pharmaceuticals, Marietta, GA) combined with 14-day courses of MPA, 10 mg/day, every 6 months. Endometrial biopsy was repeated after 1 year of the new regimen. Any vaginal bleeding was reported in each patient's daily diary. Menopause symptoms were evaluated using the Greene Menopause Symptom Index.
Results:
Among 125 women who had biopsy after 1 year of the new regimen, endometrial hyperplasia was found in two (1.6%, 95% confidence interval 0.3%, 6.2%). Of the 125 women, 44% had scheduled bleeding, and 9.4% had unscheduled bleeding. Relative to baseline vasomotor score (range 0-6), an increase of at least 2 U was reported by 20% of subjects at 6 months and by 17% of subjects at 12 months.
Conclusion:
Most women aged at least 55 years can safely switch their HRT regimen from standard dosage HRT to low-dosage estrogen opposed by MPA at 6-month intervals. Moreover, this new HRT regimen causes little vaginal bleeding while maintaining adequate control of menopausal symptoms.
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