{"paper_id":"ea861b71-eb66-4ba3-8640-95286ffe932e","body_text":"Review began\n 04/19/2024 \nReview ended\n 05/22/2025 \nPublished\n 06/01/2025\n© Copyright \n2025\nTan et al. This is an open access article\ndistributed under the terms of the Creative\nCommons Attribution License CC-BY 4.0.,\nwhich permits unrestricted use, distribution,\nand reproduction in any medium, provided\nthe original author and source are credited.\nDOI:\n 10.7759/cureus.85165\nDeeply Infiltrating Endometriosis (DIE) No More:\nDienogest as a Game Changer in Rectovaginal\nEndometriosis\nAmanda Wei Mun Tan \n, \nXin Yi Ho \n, \nJill Cheng Sim Lee \n1.\n Obstetrics and Gynaecology, KK Women's and Children's Hospital, Singapore, SGP \n2.\n Urogynaecology, KK Women’s\nand Children’s Hospital, Singapore, SGP\nCorresponding author: \nAmanda Wei Mun Tan, \namandatanwm@gmail.com\nAbstract\nRectovaginal endometriosis remains a therapeutic enigma due to its relatively low incidence and widely\ndiffering opinions on the standard of its treatment. Dienogest is a relatively novel therapy for endometriosis\nand presents major therapeutic potential in the treatment of deeply infiltrating endometriosis. This is the\ncase of a 36-year-old woman who presented to the Urogynaecology clinic with postcoital bleeding and a\nvaginal mass. She had a history of open myomectomy, removal of rectovaginal cysts, and endometriotic\ndeposits from the Pouch of Douglas one year earlier, with no treatment from then until this presentation.\nSpeculum examination revealed a 3 cm tongue-like firm mass arising from the posterior fornix with contact\nbleeding, and pelvic ultrasonography confirmed a 3.5 x 2.4 x 1.9 cm mass posterior to the cervix. The biopsy-\nproven deeply infiltrating endometriosis mass in the posterior fornix and pouch of Douglas responded well\nto oral Dienogest treatment. After three months of treatment, the patient was symptom-free, and the mass\non rectovaginal examination had shrunk to 1 cm. The endometriosis deposits were clearly demonstrated to\nbe in remission during rectovaginal examination and pelvic ultrasonography after nine months of therapy.\nThe patient experienced minimal side effects on Dienogest, namely prolonged menstrual spotting, which\nalso resolved after nine months of therapy. This is the first reported case of Dienogest successfully\nshrinking rectovaginal deeply infiltrating endometriosis from 3 cm to undetectable on ultrasound and\nvaginal examination. This case demonstrates the success of Dienogest as a therapeutic modality for\nrectovaginal endometriosis, highlighting its promising potential as a standard treatment approach in the\nlong-term management of the relapsing, chronic, and debilitating nature of endometriosis.\nCategories:\n Obstetrics/Gynecology\nKeywords:\n deeply infiltrating endometriosis, dienogest, endometriosis, rectovaginal, vaginal mass\nIntroduction\nVaginal neoplasms that belong to the group of rectovaginal deeply infiltrating endometriosis (DIE) may\nappear intimidating but are not malignant and may not even necessitate surgical resection with appropriate\ntreatment.\nEndometriosis, typically a disease in women of reproductive age, is defined as the presence of endometrial-\nlike tissue outside the uterus that responds to hormonal stimulation. It can be clinically divided into three\ndistinct forms: superficial (peritoneal/serosal), ovarian, and deep endometriosis \n[1]\n. Manifestation of\nendometriosis located more than 5 mm below the peritoneum is called DIE \n[1]\n, and it can affect the\nrectovaginal septum, rectosigmoid colon, uterosacral ligament, bladder, and ureters \n[2]\n. These lesions,\nunder the influence of oestrogen, can cause chronic inflammation, consequently forming scar tissue and\nadhesions \n[2]\n. The presentation of endometriosis is variable. Classic symptoms include chronic pelvic pain,\ndysmenorrhoea, dyspareunia, and infertility. Cyclical changes in bowel and bladder among other symptoms\ncan also arise depending on the sites infiltrated by the disease.\nThe condition is characterized by a progressive disease course with worsening symptoms if not\nappropriately managed. Women with endometriosis usually experience endometriosis-related pain,\ninfertility, or both \n[1]\n. Minimizing disease progression, alleviating symptoms such as pain, reducing\nendometriotic lesions, and improving the quality of life are therefore the cornerstones of endometriosis\nmanagement. Currently, treatment for endometriosis is categorized into medical (analgesia, hormonal\nmedications) and surgical interventions. Preferred treatment regimens, however, remain contentious,\nespecially for DIE, due to its multifocal presentation and nature of deep infiltrating nodules that can be\nsurgically challenging \n[3]\n. This necessitates the establishment of a long-term treatment algorithm to\nindividualize management and achieve the aforementioned goals of treatment, avoiding recurrent surgical\ninterventions \n[4]\n.\nDienogest, a fourth-generation progestin, is a selective progesterone receptor agonist that inhibits systemic\ngonadotrophin secretion and has no androgenic or estrogenic activity. Its antiproliferative and\n1\n1\n2\n \nOpen Access Case Report\nHow to cite this article\nTan A, Ho X, Lee J (June 01, 2025) Deeply Infiltrating Endometriosis (DIE) No More: Dienogest as a Game Changer in Rectovaginal\nEndometriosis. Cureus 17(6): e85165. \nDOI 10.7759/cureus.85165\n\nantiangiogenic properties differentiate it from other progestins in the same class. Dienogest is a relatively\nnovel treatment approach that has in recent years established itself as part of the standard medical\nmanagement of endometriosis. Its effectiveness, safety, and tolerability profile as a long-term management\nstrategy for endometriosis in routine clinical practice are increasingly being researched on a large scale, as\nshown in the VIPOS study \n[5]\n. Despite its proven efficacy in clinical trials, data regarding its long-term\ntherapeutic use, especially in Asian populations, are limited. This report describes a success story of\nrectovaginal endometriosis treated with Dienogest and its well-tolerated side effects.\nCase Presentation\nA 36-year-old woman (gravida 2, para 2) presented to the Urogynaecology Clinic with postcoital bleeding\nand a vaginal mass in June 2020. Previously, an MRI of the abdomen and pelvis done in March 2017\ndemonstrated a large uterine fibroid, bilateral endometriotic ovarian cysts, with no deep infiltrating lesions.\nShe underwent open myomectomy, removal of rectovaginal cysts, and endometriotic deposits in April 2017.\nSubsequently, she was treated with the gonadotropin-releasing hormone agonist Leuprolide Depot (Lucrin®\n11.25 mg) from March to October 2017 and levonorgestrel-releasing intrauterine system (Mirena) for five\nmonths from April to September 2018 (removed due to malposition). She has no other known medical or\nsurgical history. Her menstruation was regular with normal flow, and her cervical smears were up to date and\nnormal.\nOn representation in June 2020, she had mild dysmenorrhoea and postcoital bleeding for six months, with\notherwise regular menstruation. Rectovaginal examination revealed a 3 cm tongue-like firm mass arising\nfrom the posterior fornix with contact bleeding (Figure \n1\n). No other endometriotic deposits were noted on\nultrasound.\nFIGURE\n 1: A 3.5 x 2.4 x 1.9 cm mass arising from the posterior fornix\nduring rectovaginal examination, showing contact bleeding before\nDienogest treatment.\nThe mass was clearly seen on pelvic ultrasonography, measuring 3.5 x 2.4 x 1.9 cm posterior to the cervix\n(Figures \n2\n, \n3\n). Biopsy of the mass histologically confirmed DIE with no overt malignancy in the posterior\nfornix and Pouch of Douglas. A thorough discussion on management options was conducted with the\npatient, including conservative surveillance of DIE, oral hormonal medications such as gonadotrophin-\nreleasing hormone agonist and Dienogest, and a repeat surgery (total hysterectomy, bilateral salpingectomy\nkeep in view oophorectomy, with excision of DIE), as the patient had completed her family. The patient was\nkeen to attempt oral Dienogest 2 mg daily, which was started in June 2020.\n \n2025 Tan et al. Cureus 17(6): e85165. DOI 10.7759/cureus.85165\n2\n of \n9\n\nFIGURE\n 2: Coronal view of the posterior cervix on transvaginal\nultrasonography showing a heterogeneous structure with increased\nvascularity measuring 3.5 x 2.4 x 1.9 cm posterior to the cervix.\nFIGURE\n 3: Sagittal view of the posterior cervix on transvaginal\nultrasonography showing a heterogeneous structure with increased\nvascularity measuring 3.5 x 2.4 x 1.9 cm posterior to the cervix.\nOn follow-up after three months of oral Dienogest treatment, she reported minimal side effects of irregular\nbleeding (minimal vaginal spotting one week after starting the medication), and she was subsequently\namenorrhoeic. She also was symptom-free with no further postcoital bleeding and dysmenorrhoea. A\nrectovaginal examination demonstrated a smaller mass of approximately 1 cm in the posterior fornix (Figure\n \n2025 Tan et al. Cureus 17(6): e85165. DOI 10.7759/cureus.85165\n3\n of \n9\n\n4\n).\nFIGURE\n 4: Mass arising from the posterior fornix measuring 1 cm on\nrectovaginal examination after three months of oral Dienogest.\nAfter six months of completing Dienogest, a rectovaginal examination showed that the mass measured 0.5\ncm (Figure \n5\n) and was barely visible in the posterior fornix. The patient also reported light abnormal uterine\nbleeding of two weeks in the middle of treatment. In March 2021, after nine months of therapy, pelvic\nultrasonography and examination both demonstrated complete resolution of the vaginal endometriosis and\nendometriotic deposits in the Pouch of Douglas (Figures \n6\n, \n7\n). She also reported resolution of her prolonged\nmenstruation. Continuing of the oral Dienogest treatment was agreed upon, and since June 2020, the patient\nhas remained well and asymptomatic at two years with the physical appearance similar to that in Figure \n6\n.\n \n2025 Tan et al. Cureus 17(6): e85165. DOI 10.7759/cureus.85165\n4\n of \n9\n\nFIGURE\n 5: Mass arising from the posterior fornix measuring 0.5 cm\nduring rectovaginal examination after six months of oral Dienogest.\nFIGURE\n 6: After nine months of oral Dienogest: remission of vaginal\nendometriosis.\n \n2025 Tan et al. Cureus 17(6): e85165. DOI 10.7759/cureus.85165\n5\n of \n9\n\nFIGURE\n 7: Sagittal (left) and coronal (right) views of posterior cervix on\ntransvaginal ultrasonography post treatment showing resolution of\nvaginal endometriosis and endometriotic deposits in the Pouch of\nDouglas.\nDiscussion\nRectovaginal endometriosis remains a therapeutic challenge, with limited studies on this topic and widely\ndiffering opinions on the treatment algorithm of DIE \n[6]\n. With no permanent cure, the treatment approach\nfor DIE should be individualized. Treatment conundrums include relieving endometriotic-associated pain\nand improving fertility rates \n[1]\n. Demographics such as the patient’s age, symptoms, location of\nendometriotic deposits, and the patient’s fertility wishes and preferences are pivotal factors to consider.\nThis case illustrates the recurrence of vaginal endometriosis, possibly due to residual disease following\ninitial surgery and a limited duration of hormonal therapy. Surgical resection can eliminate visible\nendometriosis lesions but is not a curative treatment. DIE, particularly in the rectovaginal space, is often\nchallenging to excise completely, and microscopic lesions may persist despite surgical intervention \n[7]\n, with\na recurrence rate as high as 7% within two to six years after surgery \n[8]\n.\nRecurrence is common, at 40-50% at five years, especially when there is an influence of circulating\noestrogens that fuel the growth of endometriotic foci \n[9]\n. This patient received postoperative gonadotropin-\nreleasing hormone (GnRH) agonist therapy for seven months and Mirena for only five months before\nremoval due to malposition, which may have limited the long-term suppressive effect. Notably, there was a\n21-month gap without hormonal treatment, during which recurrence likely occurred, consistent with data\nshowing high relapse rates in the absence of maintenance therapy \n[10]\n.\nDIE in the posterior fornix also carries a higher risk of recurrence due to its anatomical complexity and\nhormonal responsiveness \n[11]\n. The patient’s subsequent positive response to Dienogest, with sustained\nremission and lesion resolution, aligns with evidence supporting its efficacy and tolerability for long-term\nmanagement \n[12]\n.\nCurrently, medical therapies that are approved for endometriosis include non-hormonal, non-steroidal anti-\ninflammatory drugs and hormonal therapies such as GnRH agonists, combined oral contraceptives (COC),\nand progestogens \n[1]\n. Existing literature provide evidence for the success of various medical therapies of DIE\ninvolving the bladder and bowel using danazol, GnRH agonists, and low-dose COC \n[6]\n. However, available\nreports and series studying the use of Dienogest monotherapy for deep endometriosis \n[13]\n are limited, with\nonly one demonstrating the efficacy of vaginal Dienogest in rectovaginal endometriosis \n[13]\n.\nProgestins approved for use vary between countries, including Dienogest, a relatively novel therapy for\nendometriosis. Dienogest is a progestin with highly selective progesterone activity that inhibits\n \n2025 Tan et al. Cureus 17(6): e85165. DOI 10.7759/cureus.85165\n6\n of \n9\n\ngonadotropin secretion, thereby reducing oestrogen levels and consequently causing the decidualization of\nendometrial tissue and atrophy of endometriotic lesions. Its effectiveness, safety, and tolerability profile as\na long-term management strategy for endometriosis in routine clinical practice are increasingly being\nresearched on a large scale \n[1]\n.\nIn this case report, the use of Dienogest has proven to be effective in resolving the symptoms of pain and\npostcoital bleeding in three months. It has also shown to effect reduction and even complete remission of\nthe endometriotic lesions after nine months of therapy, avoiding the need for repeat surgical intervention.\nThis finding is congruent with existing evidence that shows the improvement of symptoms before the\nreduction in size of the lesion \n[2]\n. Further, Wu et al.'s recent meta-analysis involving 256 patients illustrated\nsignificant improvement in the relief of dysmenorrhoea, dyspareunia, and pelvic pain, besides rectosigmoid\nlesion size after Dienogest monotherapy in targeting DIE \n[3]\n. In a nine-year observational study involving\n157 women, Maiorana et al. demonstrated progressive reduction in endometriotic-associated symptoms,\nmostly with dysmenorrhoea \n[14]\n. Favourable outcomes like these accentuate the need for more extensive\nresearch that can address the paucity of data that evaluate appropriate treatment strategies of DIE,\nspecifically rectovaginal endometriosis \n[2]\n, potentially redefining our current practice.\nWhile several studies have supported the effectiveness of Dienogest in symptom control, there is a scarcity\nof literature demonstrating the efficacy of the drug on regression of endometriotic lesions in DIE,\nparticularly rectovaginal endometriosis \n[2]\n. To our knowledge, available evidence is restricted to only case\nreports, most of which are on bladder endometriosis \n[15,16]\n and only one on vaginal endometriosis \n[6]\n. The\nvariable response of lesions towards the treatment may also be dependent on the differing structural features\nof endometriotic lesions \n[6]\n. Heterogeneity in the outcomes of symptom improvement is also noted in the\ncurrent evidence \n[1]\n. The proven complete resolution of the DIE lesion in this case, however, suggests the\ncurative potential of Dienogest in DIE.\nIn the battle against endometriosis, a chronic progressive disease, the safety profile of long-term medical\ntherapy is indubitably a crucial consideration. The most common adverse effect of Dienogest is observed to\nbe irregular bleeding, known to be highly associated with discontinuation of the treatment \n[6]\n. According to\na recent prospective cohort study conducted in Korea evaluating the safety profile of Dienogest for the\ntreatment of endometriosis, abnormal uterine bleeding was commonly reported in short-term use of the\ndrug. However, it tends to improve in terms of frequency and intensity with continued use of the treatment\n[17]\n. Other common adverse effects include headache, weight gain, breast tenderness, and acne. A promising\noutlook towards Dienogest is apparent from the international interest taken in further evaluation of the\nsafety profile of Dienogest monotherapy and other hormonal alternatives for endometriosis. VIPOS\n(Visanne Post-approval Observational Study) is one such ongoing large-scale long-term cohort study that is\nin the works \n[5]\n. Nonetheless, Murji’s literature review, which summarized expert recommendations from\nvarious studies, reported that Dienogest does not pose significant additional risk of breast or other types of\ncancer compared with other progestins and COC \n[18]\n.\nExisting hormonal modalities, such as GnRH agonists, have been widely used and accepted as a treatment\noption for endometriosis. However, their long-term use is associated with high risk of hypoestrogenic side\neffects and significant decrease in bone mineral density if administered without hormonal replacement\ntherapy. Conversely, Dienogest has demonstrated a favourable safety profile, as proven by high compliance\nand a low discontinuation rate secondary to adverse effects after prolonged use \n[14]\n.\nFurther, the majority of patients with endometriosis are of reproductive age; fertility is therefore an\nimportant consideration when counselling patients on the long-term management of endometriosis. While\nDienogest does not function as a contraceptive method, it provides complete ovulation inhibition if\nadministered at 2 mg daily \n[19]\n. Pharmacological data revealed a prompt return to fertility with the rapid\nresumption of ovulation (ranging 1-43 days) upon cessation of Dienogest \n[20]\n. Notably, this case reinforces\nthe importance of continuous hormonal suppression following surgery in patients with severe or deep\nendometriosis to reduce recurrence risk \n[10]\n.\nConclusions\nDIE remains a treatment conundrum for both gynaecologists and patients, with significant risks\ncomplicating surgical intervention and excision of DIE. The continual development of imaging modalities\nand increasing awareness of endometriosis and its effect on the quality of life of affected women have\ninadvertently led to the increasing incidence of deep infiltrating endometriosis. While Dienogest is\nbecoming more widely accepted as one of the mainstay medical management options for DIE, there still\nremains a scarcity in studies assessing its efficacy and its adverse reactions in the long-term in the\ntreatment of specifically rectovaginal endometriosis. The above lessons gleaned from this experience\nreinforce the need for greater sharing of outcomes and experiences of rare presentations of DIE, allowing\nfuture systematic review and reliable conclusions regarding different treatment modalities for these rare\nscenarios.\nAdditional Information\n \n2025 Tan et al. Cureus 17(6): e85165. DOI 10.7759/cureus.85165\n7\n of \n9\n\nAuthor Contributions\nAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of the\nwork.\nConcept and design:\n  \nAmanda Wei Mun Tan, Jill Cheng Sim Lee, Xin Yi Ho\nAcquisition, analysis, or interpretation of data:\n  \nAmanda Wei Mun Tan, Jill Cheng Sim Lee\nDrafting of the manuscript:\n  \nAmanda Wei Mun Tan, Jill Cheng Sim Lee, Xin Yi Ho\nCritical review of the manuscript for important intellectual content:\n  \nAmanda Wei Mun Tan, Jill Cheng\nSim Lee, Xin Yi Ho\nSupervision:\n  \nJill Cheng Sim Lee, Xin Yi Ho\nDisclosures\nHuman subjects:\n Consent for treatment and open access publication was obtained or waived by all\nparticipants in this study. \nConflicts of interest:\n In compliance with the ICMJE uniform disclosure form, all\nauthors declare the following: \nPayment/services info:\n All authors have declared that no financial support\nwas received from any organization for the submitted work. \nFinancial relationships:\n All authors have\ndeclared that they have no financial relationships at present or within the previous three years with any\norganizations that might have an interest in the submitted work. \nOther relationships:\n All authors have\ndeclared that there are no other relationships or activities that could appear to have influenced the\nsubmitted work.\nReferences\n1\n. \nBecker CM, Bokor A, Heikinheimo O, et al.: \nESHRE guideline: endometriosis\n. 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Cureus 17(6): e85165. DOI 10.7759/cureus.85165\n9\n of \n9","source_license":"CC0","license_restricted":false}