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

Boston Children's Hospital

Status and phase: Completed; Phase 2

Conditions: Endometriosis

Treatments: Drug: norethindrone acetate + placebo; Drug: Norethindrone acetate + estrogens

Study type: Interventional

Funder types: Other

Identifiers

NCT00474851

07-01-0004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 53 patients

Sex: Female

Ages: 13 to 22 years old

Volunteers: No Healthy Volunteers

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 intra-muscular 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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53 participants in 2 patient groups, including a placebo group

Norethindrone acetate + estrogens

Experimental group

Description:

Subjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + conjugated equine estrogens 0.625 mg by mouth daily for the 12 months of study participation.

Treatment:

Drug: Norethindrone acetate + estrogens

norethindrone acetate + placebo

Placebo Comparator group

Description:

Subjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + a placebo capsule by mouth daily for the 12 months of study participation.

Treatment:

Drug: norethindrone acetate + placebo