Liver function in postmenopausal women on estrogen-androgen hormone replacement therapy: A meta-analysis of eight clinical trials

Objective: To compare hepatic biochemical changes of a combined estrogen-an drogen preparation with that of estrogen alone in postmenopausal women. Design: Hepatic biochemical values from 511 surgically and 130 nonsurgicall y menopausal women being treated with hormone replacement therapy were pool ed from eight similarly designed studies performed between March 1988 and J anuary 1996 comparing esterified estrogen-methyltestosterone preparations w ith esterified estrogen, conjugated equine estrogens, and placebo controls. (1) The eight studies in this meta-analysis were controlled, randomized, mu lticenter, double-blind with identical or similar treatment arms. For hepat ic biochemistry parameters, raw data summaries and mean changes from baseli ne values with standard error (SE) were evaluated for the dosages and treat ment groups at various time periods throughout the studies. Results: Fight controlled trials involving 641 surgically and nonsurgically menopausal women were included. Changes from the pretreatment baseline val ues of liver function were compared at 1, 3, 6, 12, 18, and 24 months of th erapy. No patients demonstrated hepatotoxicity or clinically significant el evation of liver biochemistry values. None of the liver biochemistry change s measured in these studies were of clinical significance, nor were there b iochemical differences between estrogen therapy alone compared with combine d esterified estrogen-methyltestosterone preparation when administered to p ostmenopausal women during a period of up to 24 months. Conclusions: Combined esterified estrogen-methyltestosterone therapy (in do ses of 0.625 mg esterified estrogen + 1.25 mg methyltestosterone or 1.25 mg esterified estrogen + 2.5 mg methyltestosterone) was found to be safe rega rding hepatic function in postmenopausal women during the course of 24 mont hs in eight controlled clinical trials. (C) 1999, The North American Menopa use Society.