Abstract

Abstract Study question Does long-term use of dienogest reduce bone mineral density (BMD)? Is ovarian reserve after surgery a risk factor for BMD loss? Summary answer BMD was not significantly changed after long-term use of DNG for up to 8years. In patients with minimal changes, postoperative ovarian reserve were not different. What is known already Dienogest (DNG) is a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms. However, there’re some debates about the bone loss after long-term treatment. Some studies reported the BMD reduction after 2-3 years, however, predictive risk factors for BMD reduction were not found. Hypergonadotropic amenorrhea is well known risk factors for osteoporosis. Research on whether postoperative ovarian function decline is associated with osteoporosis is still lacking. Study design, size, duration This retrospective study were performed with 6180 reproductive-aged women who underwent conservative surgery for endometriomas and received postoperative dienogest (2mg/day) to prevent recurrence in the single center from May 2013 to March 2022. Among them, Sixty nine women who took DNG for more than two years after surgery and followed up BMD were enrolled for this study. Participants/materials, setting, methods Sixty nine women taking DNG for more than 24 months up to 101 months after laparoscopic operation for endometriosis were retrospectively analyzed. Calcium and vitamins were taken as supplements. The changes of BMD were evaluated every year during DNG treatment by using dual energy X-ray absorptiometry. Pain and tumor recurrence were evaluated every three months after operation. For the risk evaluation, age, BMI, tumor size and bilaterality, FSH, estradiol and AMH levels were evaluated. Main results and the role of chance Mean age of enrolled women was 39.64 ± 7.59, and mean BMI was 21.79 ± 3.51 kg/m2. Mean duration of medication was 41.33 ± 17.66 months (24-101 months). Tumor size was 5.35 ± 4.29cm. Preoperative AMH was 2.81 ± 2.07 ng/mL, postoperative AMH was 1.78 ± 2.11 ng/mL, reduction of AMH levels was 1.24 ± 1.26 ng/mL (0.0 - 4.15). Mean BMD level of femur after DNG treatment was 0.8264 ± 0.1201 g/cm2, which was not different compared to baseline (0.8404 ± 0.1194 g/cm2). BMD levels of lumbar spine were not different either after DNG treatment (baseline 0.9411 ± 0.1141 g/cm2, post-treatment 0.9477 ± 0.1346 g/cm2, separately). Only 15% of patients showed minimally decreased BMD at femur (-0.85%), mean femur BMD levels were not statistically different compared those of unchanged BMD group. Although 62.5% of patients showed a decrease in BMD at lumbar spine, mean BMD levels were not statistically different either. Postoperative FSH, estradiol and AMH levels were not significantly different between women who had reduced BMD at both site after long-term DNG use and women who did not. Limitations, reasons for caution As a retrospective study based on existing medical records, other factors that might affect the bone mineral density such as the diet, physical activity could not be assessed. Unfortunately, only a limited number of patients were included in the study as most patients received DNG for less than 2 years. Wider implications of the findings The current study contributes to enrich literature about the advantages of using DNG in a long term to prevent endometriosis recurrence. Trial registration number 2022-07-062

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