Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotropin-releasing hormone agonists: the estrogen threshold hypothesis.

Gonadotropin-releasing hormone agonists induce a reversible hypogonadotropic hypogonadal environment. Leiomyomas are common, estrogen-sensitive, benign neoplasms that decrease in size by 40% to 50% during gonadotropin-releasing hormone agonist treatment. During gonadotropin-releasing hormone agonist therapy most women are amenorrheic. After discontinuation of gonadotropin-releasing hormone agonist treatment, uterine and myoma size increase and a return to pretreatment menstrual patterns often occurs. Concerns about the safety of long-term hypoestrogenism have made long-term gonadotropin-releasing hormone agonist administration an undesirable treatment strategy. This article focuses on the use of gonadotropin-releasing hormone agonists as preoperative therapy in selected women undergoing hysterectomy or myomectomy and the combination of a gonadotropin-releasing hormone agonist with estrogen-progestin "add-back" treatment as a potential long-term medical therapy for women with symptomatic leiomyomas. Finally, an estrogen threshold hypothesis to assess the effects of circulating estrogen concentrations on different tissues, is presented.