Clinical trial NCT00474851: The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial
Official title: The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometriosis
Keywords: Endometriosis
Adolescents
Bone density
GnRH Agonist
Add-back therapy
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
First posted: 2007-05-17
Enrollment: 53
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Bone Mineral Density
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Total Body Bone Mineral Content (BMC)
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Amy D DiVasta, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.