Understanding Peritoneal Fluid Estrogen and Progesterone Concentrations Permits Individualization of Medical Treatment of Endometriosis-Associated Pain with Lower Doses, Especially in Adolescents Not Requiring Contraception

Journal article : Review

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 adolescents. Results: Oral contraceptives (OCs) were designed to inhibit ovulation in all women, and doses are much higher than the mean ovulation-inhibiting dose. Therefore, in most women, half a dose and in some women, even less is sufficient to inhibit ovulation. The inhibition of ovarian function and ovulation decreases estrogen and progesterone concentrations in plasma and peritoneal fluid. Surprisingly, the effect on peritoneal fluid steroid hormone concentrations has not been considered to explain the impact on endometriosis-associated pain. The lowering of the high estrogen concentrations in peritoneal fluid is sufficient to explain the pain decrease in superficial and ovarian endometriosis. A direct progesterone effect is unlikely, given the high progesterone concentrations in the peritoneal fluid of ovulatory women. In 8 adolescents, half an OC dose resulted in an apparently similar pain relief as a full dose (personal observation). Conclusions: The decrease in ovarian and superficial pelvic endometriosis-associated pain with OCs can be explained by lowering the intra-ovarian and the high estrogen concentrations in peritoneal fluid after ovulation. A direct progesterone effect is unlikely. Since OCs are severely overdosed in most women, half a dose is sufficient in most with fewer side effects, permitting individualization of therapy in women not requiring contraception. Understanding peritoneal fluid also explains that hormone replacement therapy is not contraindicated in most women with a history of endometriosis. Since the mechanisms of medical therapy of endometriosis-associated pain and the prevention of progression might be different, the growth of lesions must be monitored during treatment.

Authors: Koninckx, PR; Ussia, A; Adamyan, L; Wattiez, A; Vigano, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: Journal of Clinical Medicine
• Volume: 14
• Issue: 20
• Pages: 7196
• Publication date: 2025-10-12
• Acceptance date: 2025-10-09
• DOI: 10.3390/jcm14207196
• EISSN: 2077-0383
• ISSN: 2077-0383
• Pmid: 41156065
• Language: English
• Keywords: Hormone Replacement Therapy; Endometriosis; Peritoneal Fluid; Oral Contraception; GnRH; Hormonal Medical Therapy
• Subtype: Review