Effect of medroxyprogesterone on depressive symptoms in depressed and nondepressed perimenopausal and postmenopausal women after discontinuation of transdermal estradiol therapy.

Objective: Concern about adverse effects of progestins on mood has influenced the use of medroxyprogesterone (MPA) and other progestins. In this brief report, we examined whether the administration of MPA leads to depressive symptoms in two groups of perimenopausal and postmenopausal women randomly assigned to treatment with estrogen: one currently experiencing clinical depression and another without depression.

Methods: Open-label MPA 10 mg/day was administered for 14 days for endometrial protection after completion of double-blinded treatment with 17β-estradiol 0.1 mg/day for 8 to 12 weeks in 40- to 60-year-old perimenopausal and postmenopausal women enrolled in two separate randomized placebo-controlled trials for treatment of cognitive problems ("nondepressed group") or clinical depression ("depressed group"). Nonparametric tests were used to compare changes in depressive symptoms on the Beck Depression Inventory (BDI) within each group and between groups during MPA therapy.

Results: Of the 24 nondepressed (median BDI at baseline, 5.5; interquartile range [IQR], 2.5-8.5) and 14 depressed (median BDI at baseline, 17; IQR, 15-21) women treated with MPA, the BDI scores did not change during MPA treatment in either group (median change, 0; IQR, -2 to 0.5 and median, 0; IQR, -0.5 to 1.5, P = 0.28 and P = 0.50, respectively). Changes in BDI scores during treatment with MPA did not differ between groups (P = 0.25).

Conclusions: Among women receiving MPA for 2 weeks after discontinuation of estradiol, depressive symptoms did not emerge on MPA. These findings were consistent for both depressed and nondepressed women, suggesting that, even among women who are currently experiencing depression, brief treatment with MPA is unlikely to disrupt mood.