Oral Elagolix Achieves Greater Endometrioma Size Reduction and a Three-Fold Higher Conception Rate Compared to Leuprolide Depot: Indian Study
Oral Elagolix is superior to Leuprolide Depot, with a nearly three-fold higher spontaneous conception rate, greater reduction in ovarian endometrioma size, improved symptom relief, and better treatment adherence, findings from a recent study suggests.
The study is published in the April 2026 issue of The Journal of Obstetrics and Gynecology of India.
Ovarian endometriomas, also known as “chocolate cysts,” are one of its common manifestations and are reported in 17–44% of women with endometriosis.
Evolving Gonadotropin-Releasing Hormone (GnRH) Therapies with launch of oral GnRH antagonists
Long-acting GnRH agonists such as Leuprolide Depot are associated with limitations, including delayed ovulation recovery, injection-site discomfort, hypoestrogenic side effects, and poor compliance. The study therefore, assessed whether oral Elagolix, which provides immediate GnRH suppression without an initial flare-up, along with a shorter half-life and more predictable recovery of ovarian function, could be a better option for women planning natural conception shortly after treatment.
About the Study
The single-centre retrospective cohort study included 100 women with symptomatic or asymptomatic ovarian endometriomas smaller than 3 cm, patent fallopian tubes, and partners with normal semen parameters. Fifty women received oral Elagolix 200 mg twice daily for three months, while 50 received Leuprolide Depot 3.75 mg intramuscularly every 28 days for the same duration. Following a 20% dropout in the Leuprolide group, the final analysis included 50 women in the Elagolix group and 40 women in the Leuprolide group.
The groups had comparable baseline characteristics. The mean age was 30.1 ± 3.2 years in the Elagolix group and 29.9 ± 3.1 years in the Leuprolide group, while the corresponding mean cyst sizes were 2.4 ± 0.3 cm and 2.3 ± 0.4 cm. Patients were monitored monthly and followed for 12 months after treatment.
The primary outcome was spontaneous conception within 12 months of treatment cessation, while secondary outcomes included treatment adherence, symptom improvement, and reduction in endometrioma size on transvaginal ultrasonography.
The key findings from the study included:
- 20% reduction in endometrioma size: Mean cyst size decreased by 0.5 cm in the Elagolix group from a baseline mean of 2.4 cm, corresponding to an approximately 20.8% reduction. The Leuprolide group showed a mean reduction of 0.3 cm corresponding to an approximately 13% reduction.
- Nearly 3-fold higher conception rate: Spontaneous conception occurred in 36% (18/50) of women treated with Elagolix compared with 12.5% (5/40) in the Leuprolide group-an approximately 2.9-fold difference (p=0.03).
Comparing Oral Elagolix vs Inj. Leuprolide Depot for Endometrioma: Key Findings
- Better treatment adherence: All 50 women in the Elagolix group completed the three-month treatment and follow-up, resulting in 100% compliance. In comparison, the Leuprolide group had a 20% dropout rate. The researchers noted that differences in the route of administration may have contributed to the observed adherence pattern.
- Greater symptom improvement: During the 3-month treatment period, improvement in symptoms, including dysmenorrhoea and pelvic discomfort, was reported by 88% of women receiving Elagolix, compared with 72% receiving Leuprolide.
By the third month, mean Visual Analogue Scale (VAS) scores had decreased to 3.2 ± 1.1 in the Elagolix group compared with 4.5 ± 1.3 in the Leuprolide group (p=0.012). Lower pain scores were maintained in the Elagolix group throughout the 12-month follow-up period.
Practice Implications
This study reinforces the emerging shift towards oral GnRH antagonist, Elagolix, in the management of endometriosis-related infertility. These findings may apply specifically for women with ovarian endometriomas who wish to conceive naturally. Elagolix may offer a non-invasive and well-tolerated treatment option. Its rapid onset of action, oral administration, shorter duration of action, and faster hormonal recovery may be particularly relevant for fertility maintenance & better size reduction in ovarian endometrioma.
The findings support a more individualised, non-invasive, and fertility-focused approach to the management of ovarian endometriomas. As a convenient and patient-centred treatment option, Elagolix represents a promising alternative to traditional GnRH agonist, Leuprolide depot, in the context of fertility preservation and may have a role in optimising reproductive outcomes in this patient population.
Abbreviations: ART: Assisted Reproductive Technology, GnRH: Gonadotropin-Releasing Hormone, VAS: Visual Analogue Scale, TVS: Transvaginal Sonography, IVF: In Vitro Fertilization, HSG: Hysterosalpingography, MRI: Magnetic Resonance Imaging, SD: Standard Deviation, WHO: World Health Organization, β-hCG: Beta Human Chorionic Gonadotropin.
