Impact on postmenopausal symptoms of adding continuous C-21 versus C-19 progestin to estrogen

OBJECTIVE: To compare the effects of (i) continuous low dosage C-19 progestin (dl-norgestrel, NG) plus cyclical conjugated estrogen (CEE) versus (ii) continuous low dosage C-21 progestin [medroxyprogesterone acetate (MPA)] plus CEE on postmenopausal vaginal bleeding, mood and somatic, psychosomatic and psychological symptoms. METHODS: Nine hypercholesterolemic postmenopausal women with intact uteri were randomly assigned in a prospective, double-blind, two-period cross-over study of CEE (25/28 days) plus either (i) NG, (0.05 mg/day) or (ii) MPA (2.5 mg/day) for 1 year and after an appropriate wash-out period were switched to the alternative regimen for another year. Four hysterectomized control subjects received the CEE only. RESULTS: Administration of CEE + MPA versus CEE + NG resulted in a significantly higher percent of cycles which were free of vaginal bleeding (97 vs 85%), spotting (92 vs 79%) and either spotting or bleeding (92 vs 76%, P < 0.01). All three regimens significantly reduced the overall combined scores for postmenopausal somatic, psychosomatic and psychological symptoms (P < 0.05). CONCLUSIONS: Vaginal bleeding and/or spotting were significantly less frequent with CEE + MPA versus CEE + NG. However, each of the three hormonal regimens improved mood and significantly reduced postmenopausal symptoms in comparison to untreated control values.