Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate

Amy D DiVasta; Catherine Stamoulis; Jenny Sadler Gallagher; Marc R Laufer; Raymond Anchan; Mark D Hornstein

doi:10.1016/j.xfre.2021.07.003

Therapeutics · Hormonal Agents

Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate

DiVasta AD, Stamoulis C, Gallagher JS, Laufer MR, Anchan R, Hornstein MD

Published December 2021 F&S reports, 2(4), 454-461

DOI 10.1016/j.xfre.2021.07.003 PMID 34934987 PMC PMC8655411

RRM Academy Synopsis

Endometriosis pain fell on cabergoline in a nine-woman pilot trial

In a trial of nine women with endometriosis, worst pain fell 86% on cabergoline and 43% on norethindrone acetate. Cabergoline is not a hormone.

Key Findings

Nine women were randomized. One from each group left before the 6-week visit, so 3 women in the norethindrone acetate group and 4 in the cabergoline group finished 6 months.
The mean 6-month decrease in worst pain over the last 24 hours was 86% with cabergoline and 43% with norethindrone acetate. Average pain fell 83% and 57%.
On the patient global impression of change scale, 50% of the cabergoline group and 66% of the norethindrone acetate group reported moderate or high change at 6 months.
A blood marker of blood vessel growth, VEGF receptor 1, declined over 6 months with cabergoline and rose with norethindrone acetate.
No serious adverse events occurred. Of 40 symptom changes reported, 20 (50%) were mild, 17 (43%) moderate and 3 (7%) severe.

Interpretation

This randomized, double-blind trial tested cabergoline against norethindrone acetate in women with stage 1 or 2 endometriosis found at surgery. The authors note they ran no statistical tests and reported trends, since the group was small. The authors say larger trials are planned, including cabergoline added to hormone therapy.

RRM Context

The authors' introduction states that hormonal treatments do not get rid of endometriosis and that pain often rises back to baseline after they stop. Cabergoline acts on blood vessel growth in lesions. All nine women had laparoscopy-confirmed disease. RRM approaches endometriosis as a disease to find and treat at its source, with excision as the surgical standard.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To estimate the efficacy and safety of a novel nonhormonal therapeutic agent, cabergoline, compared with that of the standard clinical therapy, norethindrone acetate (NETA), for the treatment of endometriosis-associated pain in young women with endometriosis.

Design

Randomized, double-blind, placebo-controlled pilot study.

Setting

Tertiary care center.

Patients

Women (n = 9) with surgically confirmed endometriosis.

Interventions

A random, double-blind assignment to either NETA (5 mg/day) + placebo twice weekly or cabergoline (0.5 mg) twice weekly + placebo daily for 6 months.

Main Outcome Measures

We collected the measures of pelvic pain and laboratory parameters every 3 months.

Results

We observed a decrease in pain scores and increase in pain relief in women randomized to receive cabergoline, who appeared to show similar or more improvements than women treated with NETA. The serum measures of vascular endothelial growth factor receptor 1 declined over 6 months in those who received cabergoline. Cabergoline was well tolerated, and no serious adverse events occurred.

Conclusions

Safe, effective adjunct treatments are lacking for patients with endometriosis who do not respond to standard care. Because the growth of endometriosis requires angiogenesis, blood vessel growth is an attractive therapeutic target. This pilot study suggests that cabergoline, a vascular endothelial growth factor pathway inhibitor, is an effective therapeutic option for women with chronic pain due to endometriosis. Building upon this investigation, we will conduct larger, randomized trials of cabergoline, advancing research on the best treatments for endometriosis-particularly disease resistant to hormonal therapies.

Trial Registration

clinicaltrials.gov; registration number NCT02542410.

Topics

Therapeutics › Hormonal Agents › Progesterone and Progestins · General Gynecology › Pelvic Pain › Chronic Pelvic Pain · Endometriosis › Medical Management › Pain Management

Amy D DiVasta, Catherine Stamoulis, Jenny Sadler Gallagher, Marc R Laufer, Raymond Anchan, Mark D Hornstein

A DiVasta, Cathy Stamoulis, Kate Stamoulis, C Stamoulis, Jennifer Gallagher, J Gallagher, M Laufer, R Anchan, M Hornstein

PMID 34934987 34934987 DOI 10.1016/j.xfre.2021.07.003 10.1016/j.xfre.2021.07.003 DiVasta et al. 2021, DiVasta 2021

Keywords

Angiogenesis, cabergoline, endometriosis, nonhormonal therapy, norethindrone acetate

Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate

Endometriosis pain fell on cabergoline in a nine-woman pilot trial

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords