Endometriosis contributes to 5-21% of hospital admissions for pelvic pain. While hormonal therapies are pivotal in managing endometriosis-related pain, no single hormonal treatment suits all patients. We aimed to assess the effectiveness and tolerability of hormonal therapies and factors influencing response in endometriosis-associated pain treatment. Additionally, to investigate adjuvant neuromodulatory drug usage in patients who have used hormonal therapy. This cross-sectional study examined endometriosis patients undergoing hormonal therapy for pelvic pain at a tertiary referral centre for endometriosis and chronic pelvic pain (CPP). We assessed the proportion of patients reporting ineffectiveness of hormonal therapy and rates of discontinuation attributed to side effects. We evaluated factors related to treatment ineffectiveness and discontinuation due to side effects. Lastly, we determined the rates of adjuvant neuromodulatory drug use among patients who used hormonal therapy. 1011 patients were included in the study. Most hormonal therapies' ineffectiveness was related to worse CPP (P < .05). Cul-de-sac obliteration was correlated with better response to cyclic CHCs, DNG, and GnRH agonist (OR = 0.55, 95% CI [0.36 - 0.84]; OR = 0.53, 95% CI [0.29 - 0.98]; OR = 0.26, 95% CI [0.14 - 0.91], respectively). Adjuvant neuromodulatory drugs were more frequently utilized by patients who found hormone therapy ineffective except for those who used norethisterone acetate (NETA). Endometriosis pain is associated with a high chance of failed hormonal therapy. Cul-de-sac obliteration correlated with improved hormonal therapy response, highlighting the multifactorial influence on treatment outcomes. Patients who found hormone therapy ineffective tended to use adjuvant neuromodulatory drugs more frequently.
Rojas HE et al., 2026·Journal of women's health (2002)
To characterize differences between individuals with and without mid-cycle pain in a registry cohort with endometriosis. Prospective analysis of data from the Endometriosis Pelvic Pain Interdisciplinary Cohort Data Registry (Clinicaltrials.gov #NCT02911090) at a tertiary referral center in Western Canada. Three hundred forty-five individuals aged 18-49 years who: (1) had at least one episode of menstrual bleeding in the last 3 months, (2) attended a baseline initial visit, and (3) subsequently had surgery with histological confirmation of endometriosis between January 2018 and December 2023. Exclusion criteria included (1) previous hysterectomy; (2) hormonal suppressive therapy use in the last 3 months; and (3) missing data on mid-cycle pain, history of hormonal therapy use, or menstrual cycle regularity. N/A. Mid-cycle pain in the last month versus No mid-cycle pain in the last month. Of the 345 participants, 67% (n = 232) reported mid-cycle pain in the last month. Mid-cycle pain in the last month was significantly associated with higher mean Central Sensitization Inventory score (48 ± 17 versus 36 ± 16, p < 0.001) and more months of prior hormonal suppressive therapy use (58 [14-120] versus 26 [0-109], p = 0.012). Abnormal anatomy at the time of surgery (e.g., endometrioma, ovarian adhesions) was not associated with mid-cycle pain in the last month. In this endometriosis cohort at a tertiary referral center, most participants reported mid-cycle pain in the last month, which was associated with central sensitization but was not clearly related to endometriosis anatomical distortion.
Bouchard TP et al., 2026·Reproductive biomedicine online·Free to read
Do quantitative urinary hormone measurements on the Mira monitor predict and confirm ovulation accurately compared with ultrasound in women with regular menstrual cycles? Do Mira urine hormones correlate with serum hormones?
This was a prospective, single-centre, blinded diagnostic accuracy study with 52 women aged 19-44 years with regular cycles (24-38 days) who tracked 153 cycles over 18 months. Daily first-morning urine was tested with the Mira monitor for follicle stimulating hormone (FSH), oestrone-3-glucuronide (E13G), luteinizing hormone (LH) and pregnanediol glucuronide (PDG). Serial transvaginal ultrasounds (890 scans) confirmed the day of ovulation. Serum hormones were measured twice per cycle. The 121 ovulatory cycles from 49 participants with sufficient index test and reference standard data were included in the final analysis.
The Mira LH peak day strongly predicted ultrasound-confirmed ovulation (R² = 0.96, P < 0.001; intraclass correlation coefficient = 0.971), with 96% of ovulations occurring within ±1 day. The Mira PDG increase was also strongly associated with ultrasound-confirmed day of ovulation (R² = 0.87, P < 0.001). First-morning urine hormones were significantly associated with serum hormones when collected within 90 min (LH: R² = 0.92; E13G: R² = 0.73; R² = 0.61; R² = 0.75). Anovulatory cycles were identified in 11% of regularly cycling participants.
Quantitative urinary hormone monitoring with the Mira monitor provides accurate prediction and confirmation of ovulation, with strong urine-serum associations supporting reduced reliance on serial serum draws in select patients. These findings support clinical adoption of quantitative urinary fertility monitoring.
Balachandran S et al., 2026·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To assess the impact of the COVID-19 pandemic on reproductive outcomes in patients with recurrent pregnancy loss (RPL) and the influence of material and social deprivation on these outcomes.
This retrospective cohort study included RPL patients seen at a specialized clinic between March 1, 2018, and February 28, 2022. Patients were categorized into two groups based on care period: pre-pandemic (March 1, 2018-February 29, 2020) and pandemic (March 1, 2020-February 28, 2022). Cumulative probabilities of birth were estimated using the cumulative incidence function within a competing risk framework, treating pregnancy loss as a competing event. Fine and Gray regression models calculated sub-distribution hazard ratio (sHR) of birth.
544 patients were included in the study, with 255 in the pre-pandemic group and 289 in the pandemic group. Individuals in the pandemic group were less likely to achieve pregnancy than those in the pre-pandemic group (relative risk = 0.50, 95% confidence interval [CI] 0.39 - 0.66). Among those who conceived, the cumulative probability of live birth was 0.77 in both groups. Relative to individuals residing in high-social deprivation neighborhoods, those living in moderately deprived areas had higher sub-distribution hazards of live birth (adjusted sHR = 1.97, 95% CI 1.25 - 3.10; P = 0.003).
Within specialized RPL care and a universal maternity care system, pregnancy rates were lower during the first two years of the COVID-19 pandemic. However, among those who conceived, the probability of achieving a live birth remained similar between the pre-pandemic and pandemic periods.
Bouchard TP et al., 2026·Reproductive biomedicine online·Free to read
Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
Mitchell JB et al., 2022·BMC women's health·Free full text on PubMed Central
Endometriosis is a complex chronic disease that affects approximately 10% of women of reproductive age worldwide and commonly presents with pelvic pain and infertility. A systematic review of the literature was carried out using the databases Pubmed, Scopus, Cochrane and ClinicalTrials.gov in women with a confirmed laparoscopic diagnosis of endometriosis receiving progestins to determine a reduction in pain symptoms and the occurrence of adverse effects. Eighteen studies were included in the meta-analysis. Progestins improved painful symptoms compared to placebo (SMD = -0.61, 95% CI (-0.77, -0.45), P < 0.00001) with no comparable differences between the type of progestin. After median study durations of 6-12 months, the median discontinuation rate due to adverse effects was 0.3% (range: 0 - 37.1%) with mild adverse effects reported. The meta-analysis revealed that pain improvement significantly increased with the use of progestins with low adverse effects. PROSPERO CRD42021285026.
Skrzypulec V et al., 2004·Wiadomosci lekarskie (Warsaw, Poland : 1960)
The aim of this study was to evaluate the influence of the treatment with oral doses of 50 mg GnRH analogue on the intensification of endometriosis symptoms and infertility amongst women with evident symptoms of endometriosis in comparison with placebo group. A group of 34 women at the age from 18 to 45 were introduced into the study. The inclusion criteria for investigated population contained: endometriosis symptoms, endometriosis diagnosed by laparoscopy, its surgical or pharmacological treatment, negative pregnancy test score and regular menses. The patients were divided into 2 groups: investigated group and control group. Women completed "Diary" every day in which they estimated main endometriosis symptoms: dysmenorrhea, dyspareunia, pelvic pain and vaginal bleeding (according to Pain Grading Scale). The intensification of dysmenorrhea and vaginal bleeding was reduced in the investigated group in comparison with control one. These differences were statistically significant. Although the extremity of dyspareunia was decreased in two groups, this correlation was statistically significant only in the investigated group. Pelvic pain evaluation showed that its level was lower in the investigated group (p > 0.05). It was found that 11 women (investigated group) and 5 women (control group) got pregnant after the period of 12-week treatment.
GnRH analogues have an efficient influence on the reduction of endometriosis symptoms. GnRH analogues could be used in the management of infertility.
Ferrero S et al., 2018·Expert opinion on pharmacotherapy
Pharmacotherapy has a pivotal role in the management of endometriosis with long-term treatments balancing clinical efficacy (control of pain symptoms and prevention of recurrence of the disease after surgery) with an acceptable safety profile. Treatment choice is based on several factors including age and patient preference, reproductive plans, intensity of pain, severity of disease and incidence of adverse effects. The aim of this review is to provide the reader with a complete overview of drugs that are currently available or are under investigation for the treatment of endometriosis highlighting on-going clinical trials. Almost all of the available treatment options for endometriosis suppress ovarian function and are not curative. Combined oral contraceptives and progestins are commonly administered to these patients in order to ameliorate pain symptoms. Gonadotropin-releasing hormone-agonists are prescribed when first-line therapies are ineffective, not tolerated or contraindicated. Aromatase inhibitors should be reserved only for women who are refractory to other treatments. Amongst the drugs under development, gonadotropin-releasing hormone antagonists have shown the most promising results. Presently, are a number of potential therapies currently in pre-clinical or early clinical studies which may alter treatment strategies in the future although further studies are necessary.
Endometriosis is characterized by frequent recurrences of symptoms and lesions even after extirpative surgery. Because medical therapies control but do not cure the disease, long periods of pharmacologic management may be needed until pregnancy desire or, sometimes, physiologic menopause. Hormonal drugs suppress ovulation and menstruation and have similar beneficial effects against pain. However, only estrogen-progestins and progestins have safety/tolerability/cost profiles that allow long-term use. These compounds induce atrophy of eutopic and ectopic endometrium, have antiinflammatory and proapoptotic properties, and can be delivered via different modalities, including oral, transdermal, subcutaneous, intramuscular, vaginal, and intrauterine routes. At least two-thirds of symptomatic women are relieved from pain and achieve appreciable improvements in health-related quality of life. Progesterone resistance may cause nonresponse in the remaining one-third. When using estrogen-progestins continuously, individualized, tailored cycling should be explained to improve compliance. All combinations demonstrated a similar effect on dysmenorrhea, independently from progestin type. Estrogen-progestins with the lowest possible estrogen dose should be chosen to combine optimal lesion suppression and thrombotic risk limitation. Progestins should be suggested in women who do not respond or manifest intolerance to estrogen-progestins and in those with dyspareunia and/or deep lesions. Progestins do not increase significantly the thrombotic risk and generally may be used when estrogens are contraindicated. Estrogen-progestins and progestins reduce the incidence of postoperative endometrioma recurrence and show a protective effect against endometriosis-associated epithelial ovarian cancer risk.
Therapeutics › Hormonal Agents › Progesterone and Progestins · General Gynecology › Pelvic Pain › Chronic Pelvic Pain · Endometriosis › Medical Management › Hormonal Suppression Outcomes
Bahi Fayek, Yang Doris Liu, Christina Williams, Mohamed Elsibai Anter, Nasser Kamal Abdelaal, Catherine Allaire, Alaa El Halaby, Ruth Habte, Paul J Yong, Mohamed A Bedaiwy
B Fayek, Y Liu, C Williams, M Anter, N Abdelaal, Cathy Allaire, Kate Allaire, C Allaire, A Halaby, R Habte, P Yong, M Bedaiwy
PMID 40826213 40826213 DOI 10.1007/s43032-025-01947-y 10.1007/s43032-025-01947-y Fayek et al. 2025, Fayek 2025
