Progesterone effects during sequential hormone replacement therapy

Department of Clinical Sciences, Obstetrics and Gynecology, Umea University, University Hospital, S-901 87 Umea, Sweden.

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 (n=36) 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.