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Review of Hormone Replacement Therapy in Girls and Adolescents with Hypogonadism

  • Karen O. Klein
    Correspondence
    Address correspondence to: Karen O. Klein, MD, Division of Endocriology, Department of Pediatrics, University of California, San Diego and Rady Children's Hospital, Mail Code 5103, 3020 Children's Way, San Diego, CA 92123; Phone: (858) 966-4032
    Affiliations
    Division of Endocriology, Department of Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, California
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  • Susan A. Phillips
    Affiliations
    Division of Endocriology, Department of Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, California
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      Abstract

      Girls with either hypo- or hypergonadotropic hypogonadism need treatment with estrogens to initiate puberty and maintain a normal hormonal milieu. The focus of this review is hormone replacement treatment in girls with hypogonadism, to initiate and progress through puberty, and to maintain a healthy hormonal milieu in women. It also addresses what is known in the literature regarding estrogen levels in girls and women, instructive cases, practical tables for reference and application, and thoughts on future directions in this area. It represents a thorough literature review with author opinions and recommendations. Girls with normal ovarian function begin puberty on average at 10.5 years old, although there is variation according to ethnicity and degree of excess weight gain. The aim of estrogen therapy to initiate puberty is to mimic normal onset and rate of progression. On the basis of the currently available literature, when a diagnosis of hypogonadism is established, we recommend initiating treatment between age 11 and 12 years of age, with dose increases approximately every 6 months until adult levels are reached. In some situations, treatment may be delayed to allow time for diagnosis or permit more time for linear growth, or address unique risks found in girls treated for various cancers or blood disorders. When adult dosing is reached, progestins are also used to protect uterine health. This can be combined sequentially, allowing regular menstruation, or combined continuously when menstrual bleeding is not preferred. Treatment is continued until the average age of menopause, again with various considerations for longer or shorter duration on the basis of risk-benefit ratios. Transdermal estrogens are considered the most physiologic replacement and theoretically might have fewer associated risks. We review what is known about risks and outcomes and areas for future research.

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