Long-Term Effects of Gonadotropin-Releasing Hormone Agonists and Add-Back in Adolescent Endometriosis

Study Objective

To explore the potential occurrence of long-term side effects and tolerability of gonadotropin-releasing hormone agonist (GnRHa) plus 2 different add-back regimens in adolescent patients with endometriosis.

Design

Follow-up questionnaire sent in 2016 to patients who participated in a drug trial between 2008 and 2012.

Setting

Tertiary care center in Boston, Massachusetts.

Participants

Female adolescents with surgically confirmed endometriosis (n = 51) who enrolled in a GnRHa plus add-back trial as adolescents.

Interventions

Leuprolide depot 11.25 mg intramuscular injection every 3 months, plus oral norethindrone acetate 5 mg daily or oral norethindrone acetate 5 mg daily and oral conjugated equine estrogens 0.625 mg daily.

Main Outcome Measures

Side effects during and after treatment, irreversible side effects, changes in pain, overall satisfaction.

Results

The response rate was 61% (25 of 41; 10 subjects could not be located). Almost all (24 of 25) reported side effects during treatment; 80% (16 of 21) reported side effects lasting longer than 6 months after stopping treatment. Almost half (9 of 20) reported side effects they considered irreversible, including memory loss, insomnia, and hot flashes. Despite side effects, participants rated GnRHa plus add-back as the most effective hormonal medication for treating endometriosis pain; two-thirds (16 of 25) would recommend it to others. More participants who received a modified 2-drug add-back regimen vs standard 1-drug add-back would recommend GnRHa and believed it was the most effective hormonal medication.

Conclusion

Subjects believed that GnRHa used with add-back was effective and would recommend it to others, despite significant side effects. Those who received 2-drug add-back reported more success than those who received standard add-back. A subset of patients reported side effects they consider to be irreversible.