CLINICAL STUDY Progesterone effects during sequential hormone replacement therapy

Objective: The aim was to investigate the effect on mood and the physical symptoms of two dosages of natural progesterone and a placebo in postmenopausal women with and without a history of premenstrual syndrome (PMS). Design: A randomized, placebo-controlled, double-blind, crossover study was performed. Method: Postmenopausal women ðn 1⁄4 36Þ with climacteric symptoms were recruited. They received 2 mg estradiol continuously during three 28-day cycles. Vaginal progesterone suppositories with 800 mg/day, 400 mg/day, or placebo were added sequentially for 14 days per cycle. Daily symptom ratings using a validated rating scale were kept. Results: Women without a history of PMS showed cyclicity in both negative mood and physical symptoms while on 400 mg/day progesterone but not on the higher dose or the placebo. Women without a history of PMS had more physical symptoms on progesterone treatment compared with placebo. Women with prior PMS reported no progesterone-induced symptom cyclicity. Conclusion: In women without prior PMS natural progesterone caused negative mood effects similar to those induced by synthetic progestogens. European Journal of Endocrinology 148 571–577