The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial
|Endometriosis||Drug: Norethindrone acetate + estrogens Drug: norethindrone acetate + placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial|
- Bone Mineral Density [ Time Frame: Baseline to 12 months ]Adjusted mean change in total body areal bone mineral density (aBMD) over the 12 month trial
- Total Body Bone Mineral Content (BMC) [ Time Frame: Baseline to 12 months ]
|Study Start Date:||August 2007|
|Study Completion Date:||January 2015|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: 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.
Drug: Norethindrone acetate + estrogens
Norethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily
Placebo Comparator: 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.
Drug: norethindrone acetate + placebo
norethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily
Other Name: Aygestin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00474851
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Amy D DiVasta, MD, MMSc||Boston Children’s Hospital|