Analogs of Luteinizing Hormone-Releasing Hormone in the Treatment of Endometriosis

Abstract

Agonists of luteinizing hormone-releasing hormone (LHRH) induce a reversible hypoestrogenic state through the down-regulation of LHRH receptors and desensitization of the pituitary. Since endometrial implants are estrogen sensitive, LHRH agonists have frequently been used for medical treatment of endometriosis. Nowadays, LHRH agonists can be considered in general as a second-line medical treatment for endometriosis-related symptoms, as oral therapy with dienogest is as effective and has fewer side effects. However, therapy with LHRH agonists for 3-6 months prior to in vitro fertilization remains the treatment of choice in patients with endometriosis, as it significantly increases pregnancy rates. LHRH agonists are used prior to surgery and as an adjuvant after an operation to prevent recurrence or prolong disease-free intervals. Adverse effects of LHRH agonists are due to hypoestrogenism and include hot flushes, vaginal dryness, loss of libido, sleep disturbances and a diminished bone density which limits the duration of their administration to 6 months. For long-term treatment, add-back of estrogen and/or progestin,/or progestin only with or without bisphosphonates, can be used, but existing studies only cover a 12-month period of treatment. LHRH antagonists competitively block the pituitary receptors for LHRH. Consequently, a partial pharmacological hypophysectomy with a reduction of the estrogen levels to a desired level is possible if LHRH antagonists are adequately dosed. As endometriotic implants require relatively high levels of estrogen, partially lower plasma levels of estrogens are sufficient to prevent the loss of bone density. A long-term treatment without add-back therapy is also possible.