Conjugated equine estrogens (CEEs), whose brand name is Premarin, are widely used as a hormone-replacement therapy (HRT) drug to manage postmenopausal symptoms in women. Extracted from pregnant mare urine, CEEs are composed of nearly a dozen estrogens existing in an inactive sulfated form. To determine whether the hepatic steroid sulfatase (STS) is a key contributor to the efficacy of CEEs in HRT, we performed estrogen-responsive element (ERE) reporter gene assay, real-time PCR, and UPLC-MS/MS to assess the STS-dependent and inflammation-responsive estrogenic activity of CEEs in HepG2 cells and human primary hepatocytes. Using liver-specific STS-expressing transgenic mice, we also evaluated the effect of STS on the estrogenic activity of CEEs in vivo We observed that CEEs induce activity of the ERE reporter gene in an STS-dependent manner and that genetic or pharmacological inhibition of STS attenuates CEE estrogenic activity. In hepatocytes, inflammation enhanced CEE estrogenic activity by inducing STS gene expression. The inflammation-responsive estrogenic activity of CEEs, in turn, attenuated inflammation through the anti-inflammatory activity of the active estrogens. In vivo, transgenic mice with liver-specific STS expression exhibited markedly increased sensitivity to CEE-induced estrogenic activity in the uterus resulting from increased levels of liver-derived and circulating estrogens. Our results reveal a critical role of hepatic STS in mediating the hormone-replacing activity of CEEs. We propose that caution needs to be applied when Premarin is used in patients with chronic inflammatory liver diseases because such patients may have heightened sensitivity to CEEs due to the inflammatory induction of STS activity.

The aim of this study was to determine the effects of different menopausal hormone therapy regimens on body composition in healthy postmenopausal Chinese women.
One hundred and twenty-three healthy postmenopausal Chinese women were randomly assigned to either group A (0.625 mg conjugated equine estrogens [CEE] plus 100 mg micronized progesterone [MP]), group B (0.3 mg CEE plus 100 mg MP), or group C (0.625 mg CEE plus 10 mg dydrogesterone). Body composition was assessed by dual-energy X-ray absorptiometry.
One hundred and two women completed the trial at 1 year. A small but significant gain in lean body mass (619 ± 1019 g, p = 0.002) and a decrease of fat mass in all separate regions was observed in group A. A significant shift from gynoid to android fat distribution was observed in group B and group C (android/gynoid fat percentage ratios increased by 0.06 ± 0.08, p = 0.000 and 0.03 ± 0.08, p = 0.018, respectively), whereas no significant change was observed in group A (0.02 ± 0.06, p = 0.103).
In healthy postmenopausal Chinese women, 0.625 mg of CEE combined with 100 mg of MP was associated with a more favorable fat distribution compared with 0.3 mg CEE plus 100 mg MP or 0.625 mg CEE plus 10 mg dydrogesterone.