Managing Estrogen Therapy in the Pituitary Patient

Growth hormone (GH) regulates metabolic and physical health in the adult human. Because the GH system is regulated by estrogens, therapeutic estrogen compounds are likely to affect metabolic health. Estrogens are available for oral and parenteral use in natural, prodrug, and synthetic formulations including selective estrogen receptor modulators (SERMs). This review covers the pharmacology of estrogen and the effects on GH action to inform judicious use in the pituitary patient. The effects on the GH system are route dependent due to first-pass hepatic metabolism. Oral but not parenteral estrogen compounds inhibit GH action, reducing hepatic insulin-like growth factor-1 (IGF-1) production, protein anabolism, and fat utilization. In patients with GH deficiency, oral estrogen therapy exacerbates the degree of hyposomatotrophism and attenuates the beneficial effects of GH replacement therapy, effects that are greater with contraceptive than replacement doses. Surveys report that less than one-fifth of hypopituitary women are appropriately replaced by a transdermal route and up to half on oral therapy are inappropriately treated with contraceptive steroids. In acromegaly, however, estrogens, especially synthetic formulations of greater potency, reduce IGF-1, improving disease control, an effect also observed in men treated with SERMs. The route-dependent effects and potency of estrogen formulations are important considerations for optimizing the management of hypogonadal patients with pituitary disease, in particular GH deficiency and acromegaly. For hypopituitary women, estrogens should be replaced by a nonoral route. For acromegaly, oral estrogen formulations can be considered as simple adjuvant therapy for disease control.

Automated summary

Growth hormone (GH), regulated by estrogens, is important for metabolic and physical health in adults. Estrogen compounds, available in different formulations including selective estrogen receptor modulators (SERMs), can affect the GH system in a route-dependent manner due to hepatic metabolism. Oral estrogen inhibits GH action and reduces IGF-1 production, protein anabolism, and fat utilization, while parenteral estrogen does not. In patients with GH deficiency, oral estrogen therapy worsens hyposomatotrophism and attenuates the benefits of GH replacement, especially with contraceptive doses. Nonoral replacement should be considered for hypopituitary women, while oral estrogen formulations can be used as adjuvant therapy for disease control in acromegaly.