LAUSR

Abstract Disclosure: I. Murta: None. J. Bicca: None. N. Cardoso: None. Background: Endometriosis is an estrogen-dependent clinical syndrome traditionally regarded as a premenopausal condition that tends to regress after menopause. Contrary to this assumption, it can affect up to 4% of postmenopausal women. Hormone replacement therapy (HRT) in this population is challenging due to the potential reactivation of endometriotic lesions, reported in 16-22% of women aged 49-55 and a 1% risk of malignant transformation in those receiving combined HRT. Estrogen deprivation is often preferred out of concern for these complications, raising issues related to bone, cardiovascular, and metabolic health. The efficacy of HRT in this context depends on the dose, route of estrogen administration, and the type, metabolism, and progestogenic potency of the progestin used for symptom control. Clinical Case: A 54-year-old woman, SF, with no prior diagnosis of endometriosis but a long-standing history of deep dyspareunia, started presenting with hot flashes at age 47, followed by persistent pelvic pain and menorrhagia. Bone densitometry revealed osteopenia. Pelvic MRI with bowel preparation identified deep infiltrating endometriosis. Initial treatment with conventional oral progestin therapy failed to alleviate pelvic pain. She underwent surgical intervention, followed by oral progestin therapy, again with no clinical improvement. She started GnRH analog therapy with Goserelin (Zoladex), but experienced worsening vasomotor symptoms and vaginal atrophy, making the treatment poorly tolerated. After multiple failed approaches, the patient began treatment with a novel progestin (R2323) combined with low-dose transdermal estradiol (50 mcg, three times per week), which led to complete resolution of clinical symptoms and improved bone mineral density after two years of HRT. Conclusion: Although oral progestins are considered first-line therapy for endometriosis, they have a reported failure rate of 33%. GnRH agonists serve as an alternative but often induce hypoestrogenic side effects such as vasomotor symptoms and concerns regarding bone loss, particularly in menopausal patients. In this case, the progestin demonstrated antiestrogenic and antiprogestogenic activity with mild androgenic potential. Its therapeutic use led to a modest increase in bone mineral density, possibly due to this androgenic effect. Some evidence suggests that bone receptors may respond differently to this progestin's antiestrogenic action. The addition of low-dose estrogen supported metabolic and cardiovascular health. Combined HRT in patients with endometriosis should be assessed individually, considering dose, route, and type of progestin. Clinical guidelines and further clinical evidence are still needed to support decision-making regarding HRT in this population. Presentation: Monday, July 14, 2025