The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial

Condition(s) targeted: Endometriosis

Intervention: Conjugated equine estrogens (Drug); Placebo (Drug); Norethindrone acetate (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Children's Hospital Boston

Official(s) and/or principal investigator(s):
Amy D DiVasta, MD, MMSc, Principal Investigator, Affiliation: Children's Hospital Boston

Overall contact:
Amy D DiVasta, MD, MMSc, Phone: 617-355-3792, Email: amy.divasta@childrens.harvard.edu

The purpose of this study is to determine whether a regimen of norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens is superior in maintaining skeletal health and quality of life in adolescents treated with a GnRH agonist for endometriosis.

Official title: The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Bone mineral density

Secondary outcome:

Volumetric bone mineral density

Quality of life

Detailed description: Endometriosis has become increasingly recognized as a chronic illness which begins during adolescence. Untreated endometriosis may lead to chronic pain and infertility. As recognition of the need for prompt therapy increases, so does the length of time patients will be exposed to treatments. As a result, there exists a pressing need to evaluate adjunctive measures that may limit the associated negative health consequences of treatment.

A gonadotropin-releasing hormone (GnRH) agonist is one medication utilized for patients who have failed other treatments. While GnRH-agonists are effective in relieving symptoms, their long-term use is problematic. GnRH agonists induce a low-estrogen state, causing deleterious effects on bone mineralization. These negative consequences are especially important for our pediatric patients. Adolescence is the critical period in a woman's life for bone acquisition and attainment of peak bone mass. Anything that interferes with this process puts patients at risk for lifelong low bone density and future fracture.

"Add-back" therapy appears to be a promising adjunct to treatment for prevention of this bone loss. Daily therapy with low-doses of hormones preserves bone density in adult patients, without altering the efficacy of the GnRH-agonist. However, no data exist on the effect of add-back therapy in adolescents.

The aim of the current study is to evaluate the safety and efficacy of two add-back regimens, norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens, for the preservation of skeletal health and quality of life in adolescents with endometriosis treated with a GnRH-agonist.

Minimum age: 13 Years. Maximum age: 22 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Age 13-22 years, at least two years post-menarche

- Body mass index (BMI, kg/m2) between 18 -30 kg/m2

- Surgical diagnosis of endometriosis

- Clinical decision to treat with a GnRH agonist, leuprolide depot (Lupron Depot®; TAP

Pharmaceuticals, Inc.) 11. 25 mg IM every 3 months

Exclusion Criteria:

- Concomitant chronic diseases which affect bone health, such as cystic fibrosis,

inflammatory bowel disease, renal disease, or diabetes mellitus

- Markedly impaired liver function or liver failure

- Personal history of thromboembolic event (such as deep venous thrombosis)

- Medication use known to affect bone metabolism:

- Glucocorticoid therapy (including inhaled steroids) or anticonvulsants used in

the last 6 months

Amy D DiVasta, MD, MMSc, Phone: 617-355-3792, Email: amy.divasta@childrens.harvard.edu

Children's Hospital Boston, Boston, Massachusetts 02115, United States; Recruiting
Amy DiVasta, MD, Phone: 617-355-7181, Email: amy.divasta@childrens.harvard.edu

Starting date: August 2007
Last updated: June 21, 2011