
Characterized by high postpartum and postoperative recurrence rates, endometriosis requires continuous management. At a Bayer-sponsored symposium, Dr Yong-Wook Jung of Cha Gangnam Medical Center, South Korea, discussed the paradigm shift in the management of endometriosis, while Dr Pong-Mo Yuen, Director of Minimally Invasive Gynaecology at Hong Kong Sanatorium & Hospital, shared several patient cases illustrating long-term treatment with dienogest.
Challenges in diagnosis and treatment of endometriosis
The gold standard for diagnosing endometriosis traditionally involved a combination of laparoscopy and histological verification of endometrial glands, but this was associated with delays between symptom onset, diagnosis, and subsequent treatment. [Hum Reprod 2012;27:3412-3416; Hum Reprod Open 2022;2022:hoac009]
“To solve this problem, endometriosis diagnosis should be based on a combination of patient history, clinical examination, and imaging studies,” said Jung. “Such an individualized approach would reduce delays in diagnosis, provide rapid relief to affected patients, limit disease progression, and prevent sequelae.” [Nat Rev Endocrinol 2019;15:666-682; Am J Obstet Gynecol 2019;220:354.e1-354.e12]
After diagnosis, surgical management of endometriosis can lead to decreased ovarian function. Following first-line endometriosis surgery, only 40 percent of women achieve spontaneous pregnancy, which further reduces to 22 percent after repetitive surgery for recurrent endometriosis. [Fertil Steril 2009;92:1253-1255; The Obstetrician & Gynaecologist 2024;doi:10.1111/tog.12947; Front Surg 2014;doi:10.3389/fsurg.2014.00024]
In spite of surgery, disease recurrence remains a formidable challenge, with rates of 9 percent at 4 years and 28 percent at 8 years postsurgery. To prevent recurrence, postoperative hormone suppression is essential. “Hormone therapy acts like a prison that holds zombies. If you stop taking hormone therapy, the zombies will come out of the prison,” stated Jung. [J Minim Invasive Gynecol 2006;12:506-513]
The 2022 European Society of Human Reproduction and Embryology (ESHRE) guidelines recommend progestogens, such as dienogest, and combined oral contraceptives (COCs) as first-line therapies for endometriosis-related pain. [Hum Reprod Open 2022;2022:hoac009]
Efficacy and safety profile of dienogest
Dienogest is a progestin with good oral bioavailability and high selectivity for progesterone receptors, which exerts antiproliferative, anti-inflammatory and antiangiogenic effects in the endometrium and moderately suppresses circulating oestradiol and inhibits ovulation. [Womens Health (Lond) 2010;6:27-35]
A 2020 meta-analysis showed that postoperative dienogest significantly reduced the likelihood of recurrent endometriosis compared with expectant management (log odds, 1.96; p<0.001). In another meta-analysis, dienogest significantly reduced pelvic pain vs placebo at 12 months (standard mean difference [SMD], -4.31; p<0.0001) and 24 months (SMD, -3.50; p<0.0001). [J Minim Invasive Gynecol 2020;27:1503-1510; Review Reprod Sci 2023;30:3135-3143] In clinical studies, dienogest significantly reduced endometrioma cyst volume by 41 percent (p<0.005) and diameter by 40 percent (p<0.001) after 6 months of treatment. [J Obstet Gynaecol 2021;41:1246-1251; Gynecol Endocrinol 2020;36:81-83]
Regarding safety, a recent systematic review found that the majority of adverse reactions with dienogest were not serious. The most common adverse reactions included abnormal uterine bleeding (55 percent), amenorrhoea (17 percent), swelling (13 percent), and headache (8 percent). [BMC Pharmacol Toxicol 2024;25:43]
In a prospective cohort study, patients experienced improved bleeding patterns over time, with frequency and intensity of bleeding episodes decreasing with continued treatment and bleeding returning to baseline levels by 24 months. Amenorrhoea rates also increased over time. [Reprod Sci 2020;27:905-915; Reprod Sci 2022;29:1157-1169] “I would not consider this an adverse event but rather a positive outcome of the drug on endometriosis,” commented Yuen.
In terms of breast cancer risk, guidelines from the Faculty of Sexual and Reproductive Healthcare (FSRH) indicate that the limited evidence available suggests no increased risk of breast cancer associated with the use of progesterone-only pills. A study in Taiwan (n=1,080), in which dienogest was used for up to 60 months, found no association between dienogest and breast cancer. [FSRH Clinical Guideline, July 2023; Int J Gynaecol Obstet 2023;162:1114-1116]
Concerning bone health, a Japanese study found reduced bone mineral density (BMD) after 24 weeks of dienogest, but this was less profound than BMD loss associated with buserelin. In a European study, BMD reduction was observed with leuprolide, but not with dienogest. Long-term studies indicated that BMD decreases predominantly occurred in the first 6–12 months, during which depletion gradually reduced over time. [Fertil Steril 2009;675-681; Hum Reprod 2010;25:633-641; Eur J of Obstet Gynecol Reprod Bio 2017;212:9-12; Reprod Sci 2021;28:1556-1562]




