ABSTRACT
BACKGROUND: Selective serotonin-reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of depression and can be used as nonhormonal alternatives to manage hot flashes for women with a history of breast cancer and unable to take hormone replacement therapy. There are, however, few reports on the efficacy of SSRIs for the treatment of natural postmenopausal climacteric symptoms. In this pilot study, we evaluate the SSRI, fluvoxamine, for controlling climacteric symptoms and vasomotor symptoms, in particular. METHODS: Twenty-two patients were enrolled from our hospital. All were orally administered fluvoxamine (50 mg daily). Climacteric and depressive symptoms were assessed using simple menopausal index (SMI) and self-rating questionnaire for depression (SRQ-D), respectively, at baseline, and at 2 and 6 weeks post-treatment. RESULTS: Six weeks following drug administration, neither the SRQ-D nor SMI scores significantly decreased compared to baseline. The mean levels of vasomotor symptoms and mental symptoms decreased significantly following fluvoxamine administration, while skeletal muscle symptom scores did not. CONCLUSION: We were able to demonstrate that fluvoxamine was effective in treating not only depressive moods in climacteric symptoms but also the associated vasomotor symptoms. There are several limitations to this preliminary study. Future controlled studies are needed to further evaluate the efficacy of fluvoxamine for climacteric disturbances.
ABSTRACT
We report the novel observation that medroxyprogesterone acetate (MPA) attenuates the induction by 17beta estradiol (E2) of both nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) activity in human umbilical vein endothelial cells. Although MPA had no effect on basal NO production or basal eNOS phosphorylation or activity, it attenuated the E2-induced NO production and eNOS phosphorylation and activity. Moreover, we examined the mechanism by which MPA attenuated the E2-induced NO production and eNOS phosphorylation. MPA attenuated the E2-induced phosphorylation of Akt, a kinase that phosphorylates eNOS. Treatment with pure progesterone receptor (PR) antagonist RU486 completely abolished the inhibitory effect of MPA on E2-induced Akt phosphorylation and eNOS phosphorylation. In addition, the effects of actinomycin D were tested to rule out the influence of genomic events mediated by nuclear PRs. Actinomycin D did not affect the inhibitory effect of MPA on E2-induced Akt phosphorylation. Furthermore, the potential roles of PRA and PRB were evaluated. In COS cells transfected with either PRA or PRB, MPA attenuated E2-induced Akt phosphorylation. These results indicate that MPA attenuated E2-induced NO production via an Akt cascade through PRA or PRB in a non-genomic manner.
