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Abstract
The endocrine physiology of the climacteric supports a rationale for the concomitant
replacement of androgen and estrogen following menopause. Clinical and research experience
with estrogen-androgen hormone replacement therapy, as well as androgen-only therapy,
suggests that the health benefit offered by androgen replacement exceeds the potential
risk when treatment is properly managed. In this review, we concentrate on the effects
of oral alkylated androgens. The virilizing effects (eg, hirsutism, acne, voice change,
and alopecia) of oral androgens are typically dose and duration dependent; androgen
replacement at doses ≤10 mg once daily administered for prolonged periods (6 months)
produces masculinization effects that generally abate with dose reduction or discontinuation
of treatment. No clinical sequelae or irreversible pathophysiologic effects have been
associated with any virilization that may occur. Changes in lipoprotein metabolism
associated with oral estrogen-androgen use include reduced total cholesterol levels
and reduced high-density lipoprotein cholesterol levels which may reduce the long-term
risk of cardiovascular disease. No clinically identifiable risk with respect to other
cardiovascular variables, such as blood pressure, administration of low doses of oral
androgen. With regard to liver toxicity, reports of jaundice, peliosis hepatis, and
hepatocellular carcinoma are extremely rare at the dose levels of androgen used in
hormone replacement therapy, although individual sensitivity to the potential hepatotoxic
effects of oral alkylated and nonalkylated androgen may vary considerably. Daily dosing
with oral alkylated androgen in combination with estrogen is well tolerated. Retrospective
and prospective studies involving the use of androgens alone and in combination with
estrogens demonstrate that concerns about the adverse effects of androgen use associated
with supraphysiologic, self-escalated doses in men do not apply to the much lower
doses combined with estrogens for hormone replacement in postmenopausal women.
Keywords
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© 1997 Published by Elsevier Inc.
