JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):139
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263776

P-127. Impact of Congenital Generalized Lipodystrophy Type 2 on Female Reproductive Health and Response to Metreleptin Therapy: A Case Report

Michelle Moreira de Lima¹, Julliane Tamara Araújo de Melo Campos¹

¹ Universidade Federal do Rio Grande do Norte - Natal - RN - Brasil

Objective: To describe the multifaceted impact of Generalized Congenital Lipodystrophy (CGL) type 2 on female reproductive health, focusing on the morphophysiological changes resulting from subcutaneous adipose tissue deficiency, and to analyze the therapeutic response to metreleptin replacement therapy in one patient, aiming to provide support for appropriate management and improvement in the quality of life of these women.
Methods: This summary is based on a clinical case report of a patient, integrated into a book chapter that addresses the health of women with congenital lipodystrophies and the impact of adipose tissue alterations on female morphophysiology. The chapter was prepared based on a review of the scientific literature on the types of congenital lipodystrophies and their alterations in women, complemented by a multidisciplinary healthcare approach. Specific information on the patient's reproductive complications and response to treatment was obtained through her direct testimony.
Results: A 33-year-old woman was diagnosed with type 2 CGL, a rare genetic condition characterized by the abnormal distribution and generalized loss of adipose tissue from birth. This specific type of CGL is associated with pathogenic variants in the BSCL2 gene, which affect the seipin protein. The patient reported a series of significant complications related to her reproductive health, including polycystic ovary syndrome (PCOS), a dysregulated menstrual cycle, and increased menstrual flow. These manifestations are consistent with the morphophysiological changes frequently observed in women with CGL, which result from the generalized loss of subcutaneous adipose tissue. Adipose tissue, classically defined as a lipid storage tissue, has a crucial endocrine function, secreting substances such as adipokines. Leptin is vital for reproductive function, acting as a trigger signal for puberty and activating the gonadotropin pulse, responsible for changes in menstrual function and ovulation. Furthermore, hyperinsulinism, frequently present in lipodystrophic patients, contributes to excessive ovarian androgen production. For these reasons, women with CGL may experience infertility, menstrual irregularities, hyperandrogenism, hirsutism, PCOS, and increased rates of miscarriage. The patient reported having tried several medications to regulate menstrual flow without success, but only achieved significant improvement after starting metreleptin replacement therapy. Metreleptin, an analogue of the hormone leptin, is essential because CGL has low levels of this adipokine. Scientific literature corroborates that metreleptin replacement therapy normalizes gonadotropin secretion, potentially restoring reproductive function and increasing fertility, although its effects on pregnancy are not yet fully understood. In animal models, metreleptin restored reproductive function in female mice with lipodystrophy. Metreleptin has also been shown to reduce testosterone secretion without altering ovarian morphology. However, the patient emphasizes the need for ongoing support due to the multiple complications of the disease and the low-income situation of most women affected by CGL, especially in Rio Grande do Norte (RN), where GCL has a high prevalence, with approximately 32 cases per million inhabitants, in contrast to the global prevalence of 0.23 cases per million.
Conclusion: This clinical case illustrates the significant impact of congenital lipodystrophies on female reproductive morphophysiology and the effectiveness of metreleptin in managing menstrual irregularities and associated PCOS. The data confirm the need for qualified and accessible public health policies that ensure continuous, comprehensive, and comprehensive care for women with rare and complex diseases such as CGL, especially in contexts of socioeconomic vulnerability and lack of knowledge of the disease among health professionals.