Steroidal and nonsteroidal "add-back" therapy: extending safety and efficacy of gonadotropin-releasing hormone agonists in the gynecologic patient.
OBJECTIVE
To assess the efficacy of various steroidal and nonsteroidal add-back regimes in ameliorating hypoestrogenic side effects of long-term GnRH agonist (GnRH-a) therapy in gynecologic patients.


METHODS
English language literature review.


METHODS
Gynecologic patients administered GnRH-a as therapy for ovarian hyperandrogenism, premenstrual syndrome, dysfunctional uterine bleeding, uterine leiomyomata, and symptomatic endometriosis.


METHODS
Steroidal and nonsteroidal add-back regimes including estrogens with progestins, progestins alone, and progestins with organic bisphosphonates in combination with various GnRH-a for > or = 6 months of therapy.


METHODS
Vasomotor symptoms, bone density changes, lipid profiles, alterations in presenting symptoms, and disease state.


RESULTS
Estrogens in combination with progestins were efficacious as add-back in the management of ovarian hyperandrogenic states, dysfunctional uterine bleeding, premenstrual syndrome, and leiomyomata. Medroxyprogesterone acetate alone is ineffective as add-back for treatment of endometriosis or leiomyomata. Norethindrone is effective as add-back in the management of endometriosis but not leiomyomata, although high doses alter lipid profiles in an undesirable fashion. Organic bisphosphonates show great promise in preserving bone density without other untoward effects.


CONCLUSIONS
No single add-back regime is appropriate for all gynecologic indications for GnRH-a. Ideal protocols preserve the efficacy of agonists while suppressing associated vasomotor symptoms and bone density loss.
Surrey
E S
ES
Department of Obstetrics-Gynecology, University of California, Los Angeles School of Medicine, USA.
D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D004967:Estrogens / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005831:Genital Diseases, Female / Q000188:drug therapy*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D011372:Progestins / Q000008:administration & dosage* / Q000627:therapeutic use
D004164:Diphosphonates; D004967:Estrogens; D011372:Progestins; D007987:Gonadotropin-Releasing Hormone