Clinical Opinion: The Biologic and Pharmacologic Principles of Estrogen Therapy for Symptomatic Menopause

Morris Notelovitz, MD, PhD, MB, BCh, FACOG, FRCOG

In This Article


The endocrinology of the menopausal transition involves a complex interaction of molecular and tissue-specific hormone receptors, enzymes, and moderating cofactors that determine the functional expression of a given organ. The synthesis and metabolism of estrogen in estrogen-sensitive organs continue postmenopausally, albeit at levels substantially reduced from those of reproductive women. The postmenopausal production of estrogen is genetically determined. Thus, symptoms of estrogen deprivation will vary among menopausal women, although all will cease to menstruate. All prescribed estrogens have a similar class effect and exert their estrogenicity through similar genomic and nongenomic pathways. However, the source, chemical structure, and composition of the estrogens most commonly prescribed for menopausal complaints -- conjugated equine estrogens (CEE), micronized 17beta estradiol (E2), and ethinyl estradiol (EE) -- vary in content, pharmacokinetics, and pharmacodynamics. These variables are further influenced by dosage and route of administration. The net clinical effect depends on the type and amount of free bioavailable estrogen derived exogenously combined with the respective organ's endogenous synthesis of estrogen. Extrapolation of population- and group-based randomized clinical trials that evaluate a fixed dose of a standard estrogen preparation over a predetermined period of time may not be applicable to other products or to individual women whose biology differs from that of the study population. The decision to prescribe estrogen therapy for menopausal symptoms should be considered within the context of the woman's total quality of life healthcare needs and adjusted over time to ensure maximal efficacy with minimal risk.

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