First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
Menopause Unit, 2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Hormones (Athens). 2022 Sep;21(3):375-381. doi: 10.1007/s42000-022-00369-8. Epub 2022 May 9.
The cessation of ovarian function is associated with an increase in abdominal adipose tissue, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), which may contribute to the augmented cardiovascular risk observed in postmenopausal women. After ovarian function stops, circulating triglyceride, total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) concentrations increase, whereas high-density lipoprotein-cholesterol (HDL-C) and lipoprotein (Lp(a)) remain essentially unchanged. Similarly, the rates of NAFLD, possibly including the advanced forms of the disease (e.g., hepatic fibrosis), increase in postmenopausal compared with premenopausal women. These effects make menopausal hormone therapy (MHT) an attractive way to restore them. Estrogen per os decreases LDL-C and Lp(a) and increases HDL-C and triglyceride concentrations. The transdermal administration of estrogen has a more neutral effect on triglycerides, albeit a less beneficial effect on LDL-C, HDL-C, and Lp(a). Co-administration of a progestagen diminishes the effect of estrogen on LDL-C, HDL-C, and Lp(a), which, however, remains beneficial. Importantly, the effect may vary with different progestagens, being lesser with natural progesterone and dydrogesterone. Regarding the effect of MHT on NAFLD, though experimental data are currently favorable, clinical evidence is to date limited and controversial. Therefore, there is a need for specifically designed clinical trials, ideally with paired liver biopsies, to demonstrate the effect of different MHT schemes on NAFLD, which is of considerable importance, given that NAFLD is more prevalent after the cessation of ovarian function.
卵巢功能的停止与腹部脂肪组织增加、血脂异常和非酒精性脂肪肝(NAFLD)有关,这可能导致绝经后女性心血管风险增加。卵巢功能停止后,循环中的甘油三酯、总胆固醇和低密度脂蛋白胆固醇(LDL-C)浓度增加,而高密度脂蛋白胆固醇(HDL-C)和脂蛋白(Lp(a))基本不变。同样,NAFLD 的发生率,可能包括疾病的晚期形式(例如,肝纤维化),在绝经后妇女中比绝经前妇女增加。这些影响使得绝经激素治疗(MHT)成为恢复这些指标的一种有吸引力的方法。口服雌激素降低 LDL-C 和 Lp(a),并增加 HDL-C 和甘油三酯浓度。雌激素的透皮给药对甘油三酯的影响更为中性,尽管对 LDL-C、HDL-C 和 Lp(a)的影响较小。孕激素的联合应用会降低雌激素对 LDL-C、HDL-C 和 Lp(a)的作用,但仍有获益。重要的是,这种作用可能因不同的孕激素而有所不同,天然黄体酮和地屈孕酮的作用较小。关于 MHT 对 NAFLD 的影响,尽管目前实验数据有利,但临床证据有限且存在争议。因此,需要进行专门设计的临床试验,理想情况下进行配对肝活检,以证明不同 MHT 方案对 NAFLD 的影响,这非常重要,因为 NAFLD 在卵巢功能停止后更为普遍。