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.
CLINICAL
Trial Registration Number
clinicaltrials.gov; registration number NCT02542410.
PMID 34934987 34934987 DOI 10.1016/j.xfre.2021.07.003 10.1016/j.xfre.2021.07.003 DiVasta et al. 2021, DiVasta 2021
Cite this article
DiVasta, A. D., Stamoulis, C., Gallagher, J. S., Laufer, M. R., Anchan, R., & Hornstein, M. D. (2021). Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. F&S reports, 2(4), 454-461. https://doi.org/10.1016/j.xfre.2021.07.003
DiVasta AD, Stamoulis C, Gallagher JS, Laufer MR, Anchan R, Hornstein MD. Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. F&S reports. 2021;2(4):454-461. doi:10.1016/j.xfre.2021.07.003
DiVasta, A. D., et al. "Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate." F&S reports, vol. 2, no. 4, 2021, pp. 454-461.
De Cicco Nardone C et al., 2026·Archives of gynecology and obstetrics
Adenomyosis is a chronic uterine disorder characterised by ectopic endometrial tissue within the myometrium, frequently associated with dysmenorrhea, abnormal uterine bleeding (AUB), chronic pelvic pain (CPP), and dyspareunia. No standardised guidelines are currently available for its management, and therapeutic options remain limited for women seeking fertility preservation. This study aimed to evaluate the efficacy of intravaginal progesterone in alleviating adenomyosis-related symptoms in patients seeking fertility preservation. In this prospective monocentric observational study, 85 patients aged 22-50 years with ultrasound-confirmed symptomatic adenomyosis were enrolled between April 2020 and April 2024. Inclusion criteria were age 18-55 years, BMI 18-35, and a Visual Analogue Scale (VAS) score ≥ 7 for dysmenorrhea, AUB, CPP, or dyspareunia. All patients received 200 mg/day of intravaginal progesterone for 10 days per cycle. Symptom severity was assessed using VAS scores at baseline and at 6 months. Data were analysed using non-parametric statistical tests. Sixty-five patients completed the 6-month follow-up. Four patients conceived during treatment and were excluded from the final analysis. Statistically significant improvements were observed for all assessed symptoms (all p < 0.05). Median VAS scores decreased for dysmenorrhea (9 to 6, p < 0.001), AUB (8 to 6, p < 0.001), chronic pelvic pain (5.5 to 3.5, p < 0.001), and dyspareunia (2 to 0, p = 0.020). The overall treatment satisfaction was high, with a mean Likert score of 7.5 out of 10. Intravaginal progesterone appears to be an effective fertility-sparing treatment for symptomatic adenomyosis, providing significant relief across all primary symptoms, with high patient satisfaction. Larger controlled studies are warranted to confirm these preliminary findings and further define its role in clinical practice.
Anti-Infective and Anti-Inflammatory Agents · Nonsteroidal Anti-Inflammatory Drugs
Prostaglandin E2 (PGE2) is a key driver of endometriosis pathogenesis. Vipoglanstat selectively inhibits mPGES-1 enzyme activity. A Phase I trial involved 72 healthy volunteers receiving single or repeated doses, while Phase II included 69 subjects with chronic inflammatory disease receiving daily treatment. Results demonstrated the compound was safe and well tolerated at therapeutic doses and achieved complete mPGES-1 inhibition while preserving protective prostacyclin production. A Phase II endometriosis trial is scheduled to begin in 2025, focusing on pain reduction and lesion assessment via imaging.
Zhang P et al., 2023·International journal of molecular sciences
Endometriosis is an estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the uterus. Progestins are currently the most commonly used treatment for endometriosis because of their excellent therapeutic effects and limited side effects. However, progestins have been unsuccessful in some symptomatic patients. The inability of the endometrium to respond properly to progesterone is known as progesterone resistance. An increasing body of evidence suggests the loss of progesterone signaling and the existence of progesterone resistance in endometriosis. The mechanisms of progesterone resistance have received considerable scholarly attention in recent years. Abnormal PGR signaling, chronic inflammation, aberrant gene expression, epigenetic alterations, and environmental toxins are considered potential molecular causes of progesterone resistance in endometriosis. The general objective of this review was to summarize the evidence and mechanisms of progesterone resistance. A deeper understanding of how these mechanisms contribute to progesterone resistance may help develop a novel therapeutic regimen for women with endometriosis by reversing progesterone resistance.
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim of this study was to evaluate the beneficial effects of fisetin, a naturally occurring polyphenol that is frequently present in a variety of fruits and vegetables. Uterine fragments were injected intraperitoneally to cause endometriosis, and fisetin was given orally every day. At 14 days of treatment, laparotomy was performed, and the endometrial implants and peritoneal fluids were collected for histological, biochemical, and molecular analyses. Rats subjected to endometriosis presented important macroscopic and microscopic changes, increased mast cell (MC) infiltration, and fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, and volumes, as well as histological alterations, neutrophil infiltration, cytokines release, the number of MCs together with the expression of chymase and tryptase, and diminished α smooth muscle actin (α-sma) and transforming growth factor beta (TGF β) expressions. In addition, fisetin was able to reduce markers of oxidative stress as well as nitrotyrosine and Poly ADP ribose expressions and increase apoptosis in endometrial lesions. In conclusion, fisetin could represent a new therapeutic strategy to control endometriosis perhaps by targeting the MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and oxidative stress.