Dienogest in long-term management of endometriosis

24 Jun 2025 byDr. Yong-Wook Jung, Cha Gangnam Medical Center, South Korea; Dr. Pong-Mo Yuen, Director of Minimally Invasive Gynaecology, Hong Kong Sanatorium & Hospital
Dienogest in long-term management of endometriosis

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]







This featured article is supported by Bayer HealthCare Limited.
PP-VIS-HK-0087-1

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