Mitigating the economic burden of GnRH agonist therapy for progestogen-resistant endometriosis: why not?

STUDY QUESTION: Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens? SUMMARY ANSWER: An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief. WHAT IS KNOWN ALREADY: Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted. STUDY DESIGN SIZE DURATION: A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected. PARTICIPANTS/MATERIALS SETTING METHODS: Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or 'draw-back' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%). LIMITATIONS REASONS FOR CAUTION: The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed. WIDER IMPLICATIONS OF THE FINDINGS: Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. REGISTRATION NUMBER: N/A.

Association of endometriosis and adenomyosis with pregnancy and infertility.

We performed a comprehensive narrative synthesis of systematic reviews with meta-analysis published in the last 5 years on the association of endometriosis and adenomyosis with reproductive and obstetric outcomes. This review aimed to define the information on which to base preconceptional counseling and clarify whether and in which cases pregnant women with endometriosis and adenomyosis should be referred to tertiary care centers and followed as high-risk obstetric patients. Reduced pregnancy and live birth rates and an increased miscarriage rate were observed in women with endometriosis and adenomyosis. The effect was larger in women with adenomyosis than in those with endometriosis. Women with superficial peritoneal and ovarian endometriosis do not appear to be at considerably increased risk of major obstetric and neonatal complications, whereas women with severe endometriosis, whether operated or not, are at several-fold increased risk of placenta previa. Moreover, deep infiltrating endometriosis is a risk factor for spontaneous hemoperitoneum in pregnancy and is associated with surgical complications at cesarean section. Overall, women with adenomyosis are at increased risk of various adverse obstetric outcomes, including preeclampsia, preterm delivery, fetal malpresentation, postpartum hemorrhage, low birth weight, and small for gestational age. Most studies included in the considered systematic reviews are characterized by substantial qualitative and quantitative heterogeneity. This makes a reliable assessment of the available evidence difficult, and caution should be exercised when attempting to derive clinical indications. Nevertheless, women with deep infiltrating endometriosis and severe adenomyosis should be considered at high obstetric risk and can benefit from referral to tertiary care centers where they can be safely followed through pregnancy and delivery. Whether the same should apply also to pregnant women with minimal endometriosis and adenomyosis forms is currently uncertain. Emerging evidence suggests that some adverse reproductive and obstetric outcomes observed in women with endometriosis are, in fact, associated with coexisting adenomyosis.

Clinical Features and Management of Umbilical Endometriosis: A 30 Years' Monocentric Retrospective Study.

INTRODUCTION: Umbilical endometriosis (UE) is defined as the presence of endometrial-like tissue within the umbilicus and represents around 0.5-1% of all cases of endometriosis. UE is classified into primary or secondary UE. In this retrospective study, we aimed to assess symptoms, signs, recurrence rate of treated lesions, psychological wellbeing and health-related quality of life in women with UE. MATERIAL AND METHODS: We retrospectively reviewed all cases of women diagnosed with UE in the period 1990-2021 in our center. Post-operative recurrence of UE was considered as the reappearance of the umbilical endometriotic lesion, or as the recurrence of local symptoms in the absence of a well-defined anatomical recurrence of the umbilical lesion. Moreover, participants were invited to fill in standardized questionnaires on their health conditions. RESULTS: A total of 55 women with histologically proven UE were assessed in our center during the study period. At time of diagnosis, local catamenial pain and swelling were reported by 51% and 53.2% of women, respectively. A total of 46.8% of women reported catamenial umbilical bleeding. Concomitant non-umbilical endometriosis was identified in 66% of cases. As regards the treatment of UE, 83.6% of women underwent an en-bloc excision with histological confirmation of UE. During the follow-up period, 37 women (67.3%) agreed to undergo a re-evaluation. Recurrence of either umbilical symptoms, or umbilical nodule, was observed in 27% of patients, 11% of which did not receive post-operative hormonal therapy. Specifically, a recurrence of the umbilical endometriotic lesion was observed only in two women. Among the 37 women which we were able to contact for follow-up, 83.8% were satisfied with the treatment they had received. CONCLUSIONS: The high rate of patient satisfaction confirmed that surgical excision should be considered the gold standard treatment for umbilical endometriosis. Future studies should investigate the role of post-operative hormonal therapy, particularly in reducing the risk of symptom recurrence.

The Prevalence and Clinical Impact of Adenomyosis in Pregnancy-Related Hysterectomy.

BACKGROUND: The epidemiology of adenomyosis has been traditionally based on patients undergoing hysterectomy for gynecological indications, while its prevalence among hysterectomies performed for obstetric complications is unknown. The aim of this study was to assess the prevalence and clinical impact of adenomyosis diagnosed through histology among women undergoing pregnancy-related hysterectomy (PH). METHODS: This was a retrospective cohort study. Women who delivered at a tertiary care regional obstetric hub in Milan between 2009 and 2020 were reviewed to identify cases of PH. Histopathological reports of surgical specimens were examined. Cases with adenomyosis were compared to those without adenomyosis for baseline characteristics, obstetric history and outcomes. RESULTS: During the study period there were 71,061 births and a total of 130 PH, giving a PH incidence of 1.83 per 1000 deliveries. Adenomyosis cases were 18, giving a prevalence of 13.8%. Adenomyosis was associated with placenta previa (77.8 vs. 45.5%, p = 0.01), chorionamnionitis (27.8 vs. 5.4%, p = 0.008), lower gestational age at birth (32 ± 4.6 vs. 35.5 ± 3.6 weeks' gestation, p = 0.0004), and intrauterine fetal demise among twin pregnancies (50 vs. 4.5%, p = 0.048). CONCLUSION: Adenomyosis entails a relevant impact on obstetric and perinatal outcomes related to PH. More evidence is needed on the clinical relevance of an ultrasonographic diagnosis of adenomyosis before conception.

Novel pharmacological therapies for the treatment of endometriosis.

INTRODUCTION: Endometriosis is a chronic, estrogen-dependent, inflammatory disease associated with pelvic pain, infertility, impaired sexual function, and psychological suffering. Therefore, tailored patient management appears of primary importance to address specific issues and identify the appropriate treatment for each woman. Over the years, abundant research has been carried out with the objective to find new therapeutic approaches for this multifaceted disease. AREAS COVERED: This narrative review aims to present the latest advances in the pharmacological management of endometriosis. In particular, the potential role of GnRH antagonists, selective progesterone receptor modulators (SPRMs), and selective estrogen receptors modulators (SERMs) will be discussed. We performed a literature search in PubMed and Embase, and selected the best quality evidence, giving preference to the most recent and definitive original articles and reviews. EXPERT OPINION: Medical therapy represents the cornerstone of endometriosis management, although few advances have been made in the last decade. Most studies have focused on the evaluation of the efficacy and safety of GnRH antagonists (plus add-back therapy in cases of prolonged treatment), which should be used as second-line treatment options in selected cases (i.e. non-responders to first-line treatments). Further studies are needed to identify the ideal treatment for women with endometriosis.

Umbilical Endometriosis: A Systematic Literature Review and Pathogenic Theory Proposal.

Umbilical endometriosis represents 30-40% of abdominal wall endometriosis and around 0.5-1.0% of all cases of endometriosis. The aim of this systematic review is to revisit the epidemiology, signs, and symptoms and to formulate a pathogenic theory based on literature data. We performed a systematic literature review using the PubMed and Embase databases from 1 January 1950 to 7 February 2021, according to the PRISMA guidelines. The review was registered at PROSPERO (CRD42021239670). Studies were selected if they reported original data on umbilical endometriosis nodule defined at histopathological examination and described as the presence of endometrial glands and/or stromal cells in the connective tissue. A total of 11 studies (10 retrospective and one prospective), and 14 case series were included in the present review. Overall, 232 umbilical endometriosis cases were reported, with the number per study ranging from 1 to 96. Umbilical endometriosis was observed in 76 (20.9%; 95% CI 17.1-25.4) of the women included in studies reporting information on the total number of cases of abdominal wall endometriosis. Umbilical endometriosis was considered a primary form in 68.4% (158/231, 95% CI 62.1-74.1) of cases. A history of endometriosis and previous abdominal surgery were reported in 37.9% (25/66, 95% CI 27.2-49.9) and 31.0% (72/232, 95% CI 25.4-37.3) of cases, respectively. Pain was described in 83% of the women (137/165, 95% CI 76.6-88.0), followed by catamenial symptoms in 83.5% (142/170, 95% CI, 77.2-88.4) and bleeding in 50.9% (89/175, 95% CI 43.5-58.2). In the 148 women followed for a period ranging from three to 92.5 months, seven (4.7%, 95% CI 2.3-9.4) recurrences were observed. The results of this analysis show that umbilical endometriosis represents about 20% of all the abdominal wall endometriotic lesions and that over two thirds of cases are primary umbilical endometriosis forms. Pain and catamenial symptoms are the most common complaints that suggest the diagnosis. Primary umbilical endometriosis may originate from implantation of regurgitated endometrial cells conveyed by the clockwise peritoneal circulation up to the right hemidiaphragm and funneled toward the umbilicus by the falciform and round liver ligaments.

Adenomyosis: Impact on Fertility and Obstetric Outcomes.

In this commentary, we discuss the associations between adenomyosis, fertility, and obstetric outcomes. A recent meta-analysis on the impact of adenomyosis on reproductive outcomes found a 43% reduction in the odds ratio (OR) for clinical pregnancy and a threefold increase in the risk of miscarriage in women with adenomyosis compared with controls. Moreover, adenomyosis seems to be strongly associated with pre-eclampsia with an OR of almost 8. Also, the risk for small for gestational age was almost fourfold increased, whereas for preterm deliveries was threefold increased. The presence of deep infiltrating endometriosis and adenomyosis seems associated with particularly adverse obstetric outcomes, especially concerning natural conception. Some observations suggest that the probability of clinical pregnancy is considerably low in these cases, around 11.8%. Although several methodological drawbacks prevent definitive conclusions, all these elements should be considered in counseling women with adenomyosis seeking pregnancy, especially in cases of IVF.

Carbon dioxide (CO2) laser ablation of symptomatic vaginal endometriosis: a pilot study.

Deep dyspareunia affects almost half of the women with endometriosis and is associated with vaginal endometriotic lesions. Our pilot study's objective is to assess the feasibility and effectiveness of CO2-laser ablation under colposcopic guidance for the treatment of symptomatic vaginal endometriosis. A non-comparative pilot study has been performed. Only women with histologically proven vaginal endometriosis, who declared the presence of moderate or severe deep dyspareunia, resistant to at least 6 months of conventional hormonal treatment, were deemed eligible for the study. All treatments were performed in an outpatient setting with a colposcopic-guided, hand-directed CO2-laser. Variation in pain symptoms was measured with a 0- to 10-point numerical rating scale (NRS), in sexual functioning with the Female Sexual Function Index (FSFI), in psychological status with the Hospital Anxiety and Depression Scale (HADS), and in quality of life with the Short Form-12 questionnaire (SF-12). Satisfaction with treatment was evaluated according to a five-category scale (very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, very dissatisfied). Nineteen women were enrolled. No complications occurred. At 12-month follow-up, significant improvements were observed in deep dyspareunia and dyschezia scores, in FSFI, HADS, and in the physical component summary scores of SF-12, whereas the mental component score of SF-12 did not vary substantially. Most women (84%) were satisfied with the treatment received. CO2-laser ablation for vaginal endometriosis could represent a valuable alternative option for women with symptomatic lesions, both in terms of amelioration of pain symptoms and improvement in quality of life and sexual function.

Advances in the medical management of bowel endometriosis.

Endometriosis infiltrating the bowel can be treated medically in accurately selected women not seeking conception and without overt obstructive symptomatology. When the rectosigmoid junction is involved, the probabilities of intestinal symptoms relief, undergoing surgery after treatment failure, and developing bowel obstruction during hormonal treatment are around 70%, 10%, and 1-2%, respectively. When the lesion infiltrates exclusively the mid-rectum, thus in cases of true rectovaginal endometriosis, the probabilities of intestinal symptoms relief and undergoing surgery are about 80% and 3%, respectively. Endometriotic obstructions of the rectal ampulla have not been reported. A rectosigmoidoscopy or colonoscopy should be performed systematically before starting medical therapies, also to rule out malignant tumours arising from the intestinal mucosa. Progestogens are safe, generally effective, well-tolerated, inexpensive, and should be considered as first-line medications for bowel endometriosis. Independently of symptom relief, intestinal lesions should be checked periodically to exclude nodule progression during hormonal treatment.

The risk of malignancy in uterine polyps: A systematic review and meta-analysis.

BACKGROUND: Endometrial polyps are a common condition. The risk of malignancy has often led to an overtreatment with high health care costs and huge psychological distress. OBJECTIVE: We conducted a systematic review and a meta-analysis in order to estimate the prevalence of premalignant and malignant lesions in women undergoing hysteroscopic polypectomy. DATA SOURCE: We developed the search using PubMed/MEDLINE and EMBASE databases to identify papers published between 2000- January 2019. The research strategy used on Pubmed was: ("polyps" (MESH) OR "endometrial polyp*") AND ("malignancy" OR "cancer" OR "histopathology" OR "hysteroscopy" OR "ultrasound", OR "sonohysterography"). The same search was modified for EMBASE. STUDY ELIGIBILITY: We included all observational retrospective and prospective studies and studies were selected for the review if they met following inclusion criteria: pre-operative diagnosis of benign-looking endometrial polyps at ultrasound examination or at hysteroscopy, excision of endometrial polyps via surgical hysteroscopy, histopathological diagnosis of benign polyps, or hyperplasia without atypia, or premalignancy (atypical hyperplasia) or malignancy (endometrial cancer). Moreover, studies were included if number or percentage of subjects with and without malignancy was provided and if they reported data about menopausal and/or bleeding status. We excluded data presented exclusively as abstracts in national and international meetings, or case report or review articles that did not include original data and papers published in other than English language. Our primary outcome was the prevalence of endometrial premalignant or malignant polyps in the total series, among premenopausal and postmenopausal women and among women with or without abnormal bleeding and then in subgroup analysis according to study design, diagnostic method, study region and calendar year of publication. RESULTS: A total of 51 studies reporting data on 35,345 women were included in this review. The prevalence of malignant polyps was 2.73% (95% CI 2.57-2.91) with very high heterogeneity among studies. The rates were lower for premenopausal women (1.12%) than post-menopausal ones (4.93%) and the difference was statistically significant (chi-square = 397.21. p < .0001). The risk of malignancy was higher among symptomatic (5.14%) than asymptomatic ones (1.89%) (chi-square = 133.13 p < .001). We observed higher rate of malignant polyps in prospective studies. In the meta-analysis selecting 10 prospective studies the random pooled estimate was 5.88 (95% CI: 4.06-7.97) with heterogeneity among studies (heterogeneity chi square = 17.55 P = .025) whereas in retrospective studies the random pooled estimate was 2.94 (95% CI:2.24-3.71) with high heterogeneity among studies (P < .001). This finding can be due to more strict diagnostic criteria in prospective studies. CONCLUSION: Symptomatic vaginal bleeding and postmenopausal status in women with endometrial polyps increased the risk of malignancy. This finding could be an useful evidence to select patients who need to undergo hysteroscopic resection of endometrial polyps and women to whom, instead, an expectant management can be offer.

Psychosexual Consequences of Female Genital Mutilation and the Impact of Reconstructive Surgery: A Narrative Review.

Purpose: We aim to provide a comprehensive overview of the health consequences of female genital mutilation/cutting (FGM/C), with a particular focus on the psychosexual implications of this practice and the overall impact of reconstructive plastic surgery. Methods: A MEDLINE search through PubMed was performed to identify the best quality evidence published studies in English language on long-term health consequences of FGM/C. Results: Women with FGM/C are more likely to develop psychological disorders, such as post-traumatic stress disorder, anxiety, somatization, phobia, and low self-esteem, than those without FGM/C. Most studies showed impaired sexual function in women with FGM/C. In particular, women with FGM/C may be physiologically less capable of becoming sexually stimulated than uncut women. Reconstructive surgery could be beneficial, in terms of both enhanced sexual function and body image. However, prospective studies on the impact of reconstructive surgery are limited, and safety issues should be addressed. Conclusion: Although it is clear that FGM/C can cause devastating immediate and long-term health consequences for girls and women, high-quality data on these issues are limited. Psychosexual complications need to be further analyzed to provide evidence-based guidelines and to improve the health care of women and girls with FGM/C. The best treatment approach involves a multidisciplinary team to deal with the multifaceted FGM/C repercussions.

Elagolix for endometriosis: all that glitters is not gold.

Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall 'value' of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.

Perimenopausal management of ovarian endometriosis and associated cancer risk: When is medical or surgical treatment indicated?

In women with endometriosis, the lifetime risk of ovarian cancer is increased from 1.4% to about 1.9%. The risk of clear cell and endometrioid ovarian cancer is, respectively, tripled and doubled. Atypical endometriosis, observed in 1-3% of endometriomas excised in premenopausal women, is the intermediate precursor lesion linking typical endometriosis and clear cell/endometrioid tumors. Prolonged oral contraceptive use is associated with a major reduction in ovarian cancer risk among women with endometriosis. Surveillance ± progestogen treatment or surgery should be discussed in perimenopausal women with small, typical endometriomas. In most perimenopausal women with a history of endometriosis but without endometriomas, surveillance instead of risk-reducing bilateral salpingo-oophorectomy seems advisable. Risk-reducing salpingo-oophorectomy might benefit patients at particularly increased risk, but the evidence is inconclusive. Risk profiling models and decision aids may assist patients in their choice. Screening of the general perimenopausal population to detect asymptomatic endometriomas is unlikely to reduce disease-specific mortality.

Medical treatment of endometriosis-related pain.

Available medical treatments for symptomatic endometriosis act by inhibiting ovulation, reducing serum oestradiol levels, and suppressing uterine blood flows. For this, several drugs can be used with a similar magnitude of effect, in terms of pain relief, independently of the mechanism of action. Conversely, safety, tolerability, and cost differ. Medications for endometriosis can be categorized into low-cost drugs including oral contraceptives (OCs) and most progestogens, and high-cost drugs including dienogest and GnRH agonists. As the individual response to different drugs is variable, a stepwise approach is suggested, starting with OCs or low-cost progestogens, and stepping up to high-cost drugs only in case of inefficacy or intolerance. OCs may be used in women with dysmenorrhea as their main complaint, and when only superficial peritoneal implants or ovarian endometriomas <5 cm are present, while progestogens should be preferred in women with severe deep dyspareunia and when infiltrating lesions are identified.

Medical treatment in the management of deep endometriosis infiltrating the proximal rectum and sigmoid colon: a comprehensive literature review.

A comprehensive literature review was performed to evaluate the effect of various hormonal therapies, in terms of variations of intestinal and pain complaints and of patient satisfaction with treatment, in women with symptomatic, non-severely sub-occlusive endometriosis infiltrating the proximal rectum and sigmoid colon. A MEDLINE search through PubMed from 2000 to 2018 was conducted to identify all original English language articles published on medical treatment for colorectal endometriosis. Additional reports were identified by systematically reviewing reference lists and using the "similar articles" function in PubMed. A total of 420 women with colorectal endometriosis treated with combined oral contraceptives, progestins, gonadotropin releasing-hormone (GnRH) agonists and aromatase inhibitors have been described in eight case series, two retrospective cohort studies and four case reports. Published data consistently suggest that several hormonal medications can control most symptoms associated with intestinal endometriosis, provided the relative bowel lumen stenosis is less than 60%. Patients with irritative-type symptoms appear to respond better than those with constipation. Overall, about two-thirds of women were satisfied with the treatment received, independently of the drug used. Progestins are the compound supported by the largest body of evidence. The addition of aromatase inhibitors or, alternatively, the use of GnRH agonists does not seem to be associated with better outcomes. Long-term treatment with a progestin should be proposed as an alternative to surgery to patients with non-severely sub-occlusive endometriosis infiltrating the proximal rectum and sigmoid colon who are not seeking conception. The final decision should be shared together with the woman, respecting her preferences and priorities.

Is Shifting to a Progestin Worthwhile When Estrogen-Progestins Are Inefficacious for Endometriosis-Associated Pain?

The purpose of this study was to assess the proportion of patients satisfied with their treatment after a change from a low-dose oral contraceptive (OC) to norethisterone acetate (NETA) because of inefficacy of OC on pain symptoms. To this end, prospective, self-controlled study was conducted on 153 women using OC as a treatment for endometriosis and with persistence of one or more moderate or severe pain symptoms. At baseline and during 12 months after a shift from OC to oral NETA, 2.5 mg/d, pelvic pain was measured by means of a 0- to 10-point numerical rating scale and a multidimensional categorical rating scale. Variations in health-related quality of life, psychological status, and sexual function were also evaluated with validated scales. At the end of the study period, participants indicated the degree of satisfaction with their treatment according to a 5-degree scale from very satisfied to very dissatisfied. A total of 28 women dropped out of the study, the main reason was intolerable side effects (n = 15). At 12-month assessment, 70% of participants were very satisfied or satisfied with NETA treatment (intention-to-treat analysis). Statistically significant improvements were observed in health-related quality of life, psychological status, and sexual function. At per-protocol analysis, almost half of the patients (58/125) reported suboptimal drug tolerability. However, complaints were not severe enough to cause dissatisfaction, drug discontinuation, or request for surgery. These encouraging results could be used to counsel women with symptomatic endometriosis not responding to OC and to inform their decisions on modifications of disease management.