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Estrogen Replacement in Women of Fertile Years with Hypopituitarism

Division of Clinical Sciences (North) (P.M.M., J.W., R.J.M.R.), University of Sheffield, Sheffield S5 7AU, United Kingdom; KIGS/KIMS/Acrostudy Medical Outcomes (Pfizer Endocrine Care) (P.J., M.K.-H.), Stockholm, Sweden; Riks Hospitalet (U.F.-R.), Copenhagen, DK-2100 Denmark; and Department of Pharmacy (M.K.-H.), Uppsala University, Uppsala, Sweden

Address all correspondence and requests for reprints to: Prof. R. J. M. Ross, Clinical Sciences Center, Northern General Hospital, Sheffield, United Kingdom S5 7AU. E-mail: r.j.ross{at}sheffield.ac.uk.

Background: What form of estrogen to prescribe a young hypopituitary woman with gonadal failure remains an open question despite evidence that oral estrogen therapy induces GH resistance and an increase in fat mass.

Methods: Using an international surveillance study of hypopituitary patients, we examined two questions: 1) What estrogen is prescribed to young women of fertile years with hypopituitarism? 2) Is there a difference in body composition or IGF-I levels dependent on the type of estrogen prescribed?

Results: Six hundred twenty-eight GH-deficient women, aged 18–50 yr, were identified. Three hundred thirteen had normal gonadal function, and 315 were receiving estrogen therapy; of these 14% were using transdermal estradiol, and 86% were taking an oral estrogen preparation (38% oral estradiol, 18% conjugated estrogens, and 30% ethinyl estradiol in the oral contraceptive). There was no difference in weight, waist/hip ratio, or body composition between the women taking different estrogen therapies. However, if the oral estrogen groups were combined, they showed less change in waist and hip measurement and had a greater waist/hip ratio after 1 yr of GH treatment compared with patients with normal gonadal function (0.85 vs. 0.83; P = 0.022). Patients taking ethinyl estradiol had lower age-adjusted IGF-I SD scores and required almost twice the GH dose to achieve an IGF-I SD score that remained lower than patients with normal gonadal function and patients receiving transdermal estradiol.

Conclusions: 1) The majority of women of fertile years with hypo-pituitarism take oral estrogen replacement therapy. 2) Waist/hip ratio was greater in women taking oral estrogens, and there is indirect evidence that oral estrogens reduce the action of GH on fat mass. 3) Patients using the oral contraceptive had lower IGF-I levels and required twice the GH dose compared with patients receiving transdermal estradiol.

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