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

NCT ID: NCT00474851

Last Updated: 2015-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2015-01-31

Brief Summary

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.

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.

Conditions

Endometriosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Norethindrone acetate + estrogens

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.

Group Type: EXPERIMENTAL

Norethindrone acetate + estrogens

Intervention Type: DRUG

Norethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily

norethindrone acetate + placebo

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.

Group Type: PLACEBO_COMPARATOR

norethindrone acetate + placebo

Intervention Type: DRUG

norethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily

Interventions

Norethindrone acetate + estrogens

Norethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily

Intervention Type: DRUG

norethindrone acetate + placebo

norethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily

Intervention Type: DRUG

Other Intervention Names

Aygestin; Premarin; Aygestin

Eligibility 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 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

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 22 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Amy DiVasta

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amy D DiVasta, MD, MMSc

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Children's Hospital Boston

Boston, Massachusetts, United States

Countries

United States

References

Gallagher JS, DiVasta AD, Vitonis AF, Sarda V, Laufer MR, Missmer SA. The Impact of Endometriosis on Quality of Life in Adolescents. J Adolesc Health. 2018 Dec;63(6):766-772. doi: 10.1016/j.jadohealth.2018.06.027.

Reference Type: DERIVED

PMID: 30454733 (View on PubMed)

DiVasta AD, Feldman HA, Sadler Gallagher J, Stokes NA, Laufer MR, Hornstein MD, Gordon CM. Hormonal Add-Back Therapy for Females Treated With Gonadotropin-Releasing Hormone Agonist for Endometriosis: A Randomized Controlled Trial. Obstet Gynecol. 2015 Sep;126(3):617-627. doi: 10.1097/AOG.0000000000000964.

Reference Type: DERIVED

PMID: 26181088 (View on PubMed)

Other Identifiers

07-01-0004

Identifier Type: -

Identifier Source: org_study_id