Comparison of quality of life in patients with endometriosis undergoing treatment with progestins, oral contraceptives pills (OCP), and GnRH agonists

This prospective observational and comparative study employed a census sampling approach, enrolling all eligible patients diagnosed with endometriosis at Amir al-Momenin Hospital (Zabol, Iran) between 2022 and 2024. The diagnosis was confirmed by a team of gynecologists who utilized a variety of diagnostic imaging modalities, including transvaginal ultrasound (TVS), transrectal ultrasound (TRS), and magnetic resonance imaging (MRI). The participants included in the study were diagnosed with endometriosis based on imaging findings, using one or more of the following modalities: transvaginal ultrasound (TVS), transrectal ultrasound (TRS), or magnetic resonance imaging (MRI). The selection of imaging modality was made on the basis of clinical presentation and anatomical accessibility, in accordance with standard gynecological practice. The diagnostic criteria have been specified as including typical imaging features of endometriosis, such as the presence of ovarian endometriomas with ground-glass echogenicity on TVS/MRI, deep infiltrating lesions involving the uterosacral ligaments, rectovaginal septum, or bladder, as well as indirect signs including adhesions and fixed retroverted uterus. Patients were eligible for the study if they were aged 18–45 years, had not received prior treatment with progestins, OCPs, or GnRH agonists, and exhibited endometriosis-related symptoms (e.g., pelvic pain, dysmenorrhea, or dyspareunia) with a VAS score above 6. Furthermore, eligible patients exhibited a willingness to participate, a lack of desire for fertility, and an absence of medical history pertaining to uterine fibroids, adenomyosis, or uterine anomalies. Patients who did not complete follow-ups, experienced severe drug-related side effects requiring discontinuation, had a revised diagnosis during the study, or became pregnant were excluded from the study. The collection of data was executed at a single time point, which occurred subsequent to a minimum of three months of uninterrupted treatment with OCPs, progestins, or GnRH agonists. All participants had received continuous treatment with OCPs, progestins, or GnRH agonists for a minimum of three months prior to completing the EHP-30 questionnaire. The present time point was selected to ensure sufficient therapeutic exposure for a meaningful assessment of treatment effects on quality of life. Patients who discontinued treatment prior to reaching the 3-month point were excluded from the final analysis. The duration of treatment varied from three to 12 months, contingent on individual follow-up and medication tolerance. However, the quality of life evaluation was standardized at the three-month follow-up for all groups. At this juncture, the Endometriosis Health Profile-30 (EHP-30) questionnaire was self-administered by the patients during their routine follow-up visit at the outpatient gynecology clinic. Trained study personnel were available to provide clarification if needed, but no part of the questionnaire was interviewer-administered. At the onset of the study, demographic and medical history data were collected using a structured, researcher-designed questionnaire. This questionnaire was completed by the study staff through patient interviews. Quality of life was assessed via the Endometriosis Health Profile-30 (EHP-30) questionnaire. The EHP-30 comprises 30 items across five domains: pain, control/powerlessness, emotional well-being, social support, and self-perception. Participants were asked to respond on a five-point Likert scale. The validity and reliability of the Persian version of the EHP-30 had previously been established by Najomi et al. [ 19 ]. All analyses were performed using SPSS version 26. Prior to enrollment, patients provided written informed consent after receiving detailed explanations of the study’s objectives and procedures. The study protocol received ethical approval from Zabol University of Medical Sciences (IR.ZBMU.REC.1404.010). Written informed consent was obtained from all participants prior to enrollment, and all procedures adhered to the Declaration of Helsinki.

A total of 135 women were included in the study across three treatment groups: oral contraceptive pills (OCPs, n  = 39), progestins ( n  = 74), and gonadotropin-releasing hormone (GnRH) agonists ( n  = 22). The baseline characteristics, including age, weight, height, and age at first intercourse, are summarized in Table  1 . The mean age of participants was comparable across the three groups (OCPs: 32.38 ± 8.12 years, progestins: 32.08 ± 7.45 years, GnRH: 34.42 ± 7.73 years; p  = 0.822). Similarly, no statistically significant differences were observed between the groups in terms of weight ( p  = 0.113), height ( p  = 0.137), or age at first intercourse ( p  = 0.120). Table 1 Baseline characteristics of participants in the ocps, progestin, and GnRH agonist groups, including age, weight, height, and age at first intercourse. Abbreviations: ocps = oral contraceptive pills; sd = standard deviation Variable OCPs Progestin GnRH agonist P -value Age(year) 32.38 ± 8.12 32.08 ± 7.45 34.42 ± 7.73 0.822 Weight(Kg) 63.36 ± 16.27 68.19 ± 28.11 67.50 ± 18.77 0.113 Height(CM) 160.52 ± 6.20 154.78 ± 27.93 162.30 ± 8.06 0.137 Age First intercourse(year) 22.27 ± 5.22 20.94 ± 5.72 23.40 ± 6.21 0.120 Baseline characteristics of participants in the ocps, progestin, and GnRH agonist groups, including age, weight, height, and age at first intercourse. Abbreviations: ocps = oral contraceptive pills; sd = standard deviation Table  2 outlines the demographic and lifestyle characteristics of the study population. There were no statistically significant differences among the groups with regard to occupation ( p  = 0.648), education level ( p  = 0.905), marital status ( p  = 0.473), physical activity ( p  = 0.325), coffee consumption ( p  = 0.627), hookah use ( p  = 0.792), cigarette smoking ( p  = 0.699), or alcohol use ( p  = 0.236). However, a statistically significant difference in nutritional status was found across the groups ( p  = 0.019), with the GnRH group exhibiting slightly lower rates of normal nutrition compared to the others. Table 2 Distribution of demographic and behavioral characteristics among the ocps, progestin, and GnRH agonist groups. Includes education, marital status, nutrition, and lifestyle factors Variable OCPs Progestin GnRH agonist P -value Job unemployed - 1(1.4) - 0.648 student 2(5.1) 3(4.1) 1(4.5) housewife 28(71.8) 52(70.3) 15(68.2) employee 5(12.8) 7(9.5) 3(13.6) worker 2(5.1) 5(6.8) 2(9.1) self-employee 2(5.1) 4(5.4) 1(4.5) medical staff - 2(2.7) - Education illiterate 7(17.9) 12(16.2) 4(18.2) 0.905 primary Education 11(28.2) 24(32.4) 8(36.4) High school/Diploma 10(25.6) 11(14.9) 3(13.6) graduate 3(7.7) 5(6.8) 3(13.6) Marriage Status single 9(23.1) 16(21.6) 7(31.8) 0.473 married 30(76.9) 54(73) 15(68.2) divorced - 3(4.1) - widow - 1(1.4) - Exercise Yes 7(17.9) 15(20.3) 6(27.3) 0.325 No 32(82.1) 59(79.7) 16(72.7) Nutrition normal 36(92.3) 69(93.2) 20(90.9) 0.019 vegetarian 2(5.1) 2(2.7) 1(4.5) Meat & protein 1(2.6) 1(1.4) 1(4.5) Coffee per Day Yes 10(25.6) 16(21.6) 6(27.3) 0.627 No 29(74.4) 58(78.4) 16(72.7) Hookah Yes 6(15.4) 6(8.1) 21(95.5) 0.792 No 32(97.4) 66(89.2) 1(4.5) Smoking never 10(25.6) 13(17.6) 3(13.6) 0.699 smoker 5(12.8) 4(5.4) 12(54.5) Rare Smoker 18(46.2) 42(56.8) 15(68.2) Alcohol Non-Drinker 32(82.1) 66(89.2) 19(86.4) 0.236 Drinker 1(2.6) 1(1.4) 3(13.6) EX-Drinker 1(2.6) - - Distribution of demographic and behavioral characteristics among the ocps, progestin, and GnRH agonist groups. Includes education, marital status, nutrition, and lifestyle factors The prevalence of various gynecological and general health conditions among the participants is presented in Table  3 . Most health-related variables showed no statistically significant differences among the groups. However, dyschezia was significantly more common in the progestin group compared to the GnRH group ( p  = 0.037), and psychological disorders also differed significantly among the groups ( p  = 0.019), with a higher prevalence observed in the OCP group. Table 3 Health-related variables including menstrual symptoms and disease history in the ocps, progestin, and GnRH agonist groups Variable OCPs Progestin GnRH agonist P -value Menstruation Regular 28(71.8) 55(77) 17(77.3) 0.983 irregular 10(25.6) 16(21.6) 5(22.7) Spotting yes 20(51.3) 37(50) 9(40.9) 0.431 NO 19(48.7) 36(48.6) 12(54.5) Dysmenorrhea yes 37(94.9) 71(95.9) 21(95.5) 0.869 NO 2(5.1) 3(4.1) 1(4.5) Pelvic Pain yes 34(87.2) 67(90.5) 19(86.4) 0.943 NO 5(12.8) 7(9.5) 3(13.6) Dyschezia yes 12(30.8) 25(33.8) 4(18.2) 0.037 NO 26(66.7) 49(66.2) 18(81.8) Hematochezia yes 3(7.7) 2(2.7) 2(9.1) 0.913 NO 36(92.3) 72(97.3) 20(90.9) Hematuria yes 3(7.7) 2(2.7) - 0.125 NO 36(92.3) 72(97.3) 22(100) Diarrhea yes 3(7.7) 4(5.4) 3(13.6) 0.444 NO 36(92.3) 69(93.2) 19(86.4) Depression and Anxiety yes 18(46.2) 36(48.6) 14(63.6) 0.322 NO 21(53.8) 37(50) 7(31.8) Allergy yes 5(12.8) 5(6.8) 4(18.2) 0.473 NO 32(82.1) 67(90.5) 17(77.3) Hypertension yes 2(5.1) 7(9.5) 3(13.6) 0.235 NO 37(94.9) 67(90.5) 19(86.4) Neurologic Disease yes 2(5.1) 5(6.8) - 0.253 NO 36(92.3) 68(91.9) 22(100) Cardiovascular Disease yes 1(2.6) 5(6.8) 1(4.5) 0.215 NO 38(97.4) 69(93.2) 21(95.5) Psychologic Disease yes 4(10.3) 1(1.4) 2(9.1) 0.019 NO 35(89.7) 72(97.3) 20(90.9) Hematologic Disease yes 7(17.9) 5(6.8) 3(13.6) 0.151 NO 32(82.1) 69(93.2) 19(86.4) Endocrine Disease yes 6(15.4) 7(9.5) 5(22.7) 0.07 NO 33(84.6) 67(90.5) 17(77.3) Nephrology Urologic Disease yes 6(15.4) 6(8.1) 1(4.5) 0.069 NO 33(84.6) 68(91.9) 21(95.5) Headache yes 10(25.6) 14(18.9) 4(18.2) 0.916 NO 29(74.4) 60(81.1) 18(81.8) Muscular Pain yes 6(15.4) 7(9.5) 2(9.1) 0.364 NO 33(84.6) 67(90.5) 20(90.9) Health-related variables including menstrual symptoms and disease history in the ocps, progestin, and GnRH agonist groups The mean scores of quality of life were 88.68 ± 26.17 for the OCP group, 89.56 ± 39.85 for the progestin group, and 105.25 ± 31.66 for the GnRH group (Table  4 ). Although the GnRH group had higher average scores, this difference did not reach statistical significance ( p  = 0.197). Table 4 Mean and standard deviation of quality of life scores among the ocps, progestin, and GnRH agonist groups. Abbreviations: sd = standard deviation Variable OCPs Progestin GnRH agonist F P -value Quality of Life 88.68 ± 26.17 89.56 ± 39.85 105.25 ± 31.66 1.65 0.197 Mean and standard deviation of quality of life scores among the ocps, progestin, and GnRH agonist groups. Abbreviations: sd = standard deviation GnRH Agonists: The most common side effects reported were hot flashes, vaginal dryness, and mood swings, typically starting within 4 to 6 weeks of treatment initiation. These symptoms reflect the hypoestrogenic state induced by this therapy. Progestins: Patients frequently reported breakthrough bleeding, mood changes, and breast tenderness, with onset usually within the first 1 to 2 months of treatment. OCPs: The most prevalent side effects included nausea, headaches, and breast tenderness, commonly appearing within the first month of use.

The present study revealed that all three treatments examined—progestins, OCPs, and GnRH agonists—exhibited comparable effects on the quality of life of patients diagnosed with endometriosis. However, the observed differences in some demographic and psychological health variables suggest that attention to factors beyond drug treatment is essential to improving the quality of life for these patients. Future research should concentrate on the impact of these complementary factors (e.g., mental health and nutrition) on improving the quality of life in patients with endometriosis. Moreover, the selection of treatment modalities should be informed by a collaborative decision-making process that incorporates the patient’s preferences and unique conditions.

In this study, the quality of life of patients with endometriosis undergoing treatment with progestins, OCPs, and GnRH agonists was examined. Based on the results, no significant difference in the quality of life was observed between the different treatment groups. This suggests that none of these treatments significantly outperform the others in improving quality of life. Although the difference in quality of life between the GnRH group and the other two groups was not statistically significant, it may be related to the side effects associated with this treatment, such as early menopause symptoms. These findings align with a systematic review conducted by Ambacher and colleagues, which showed that the use of subcutaneous progestin implants could improve the quality of life of patients [ 19 ]. However, as noted by Ambacher, several limitations such as small sample size and data heterogeneity could make it difficult to draw definitive conclusions. In our study, no significant difference in quality of life was observed between the treatment groups ( P  = 0.197), which may also be due to similar limitations in sample size and patient diversity. In the study by Canday and Salman, which investigated the efficacy of oral contraceptives and diogest, focusing on the quality of life scale, it was found that there were no significant differences between the two drug groups in terms of education status, body mass index, family history, smoking and alcohol consumption, and age ( p  > 0.05). Furthermore, no significant difference was observed in the quality of life before and after treatment ( p  > 0.05), which is consistent with our findings [ 20 ]. The clinical trial conducted by Gallagher and colleagues also examined the effects of GnRH agonists combined with supplemental treatment on the quality of life of adolescents with endometriosis. The results showed that treatment with a combination of GnRH agonists and hormonal supplementation improved the quality of life of adolescents with endometriosis [ 21 ]. In a review study by Barbara and colleagues, which examined the benefits and drawbacks of existing drugs for the medical treatment of endometriosis on the quality of life of these patients, it was suggested that the choice of medication for pain associated with endometriosis should consider not only effectiveness but also side effects, tolerability, adherence to treatment, and women’s preferences. Shared decision-making (a medical approach in which doctors and patients actively collaborate on treatment decisions) should guide the selection of the most appropriate treatment [ 13 ]. In our study, significant differences were found between the three groups in terms of psychological diseases, nutritional status, and Dyschezia. A study by Haaps and colleagues also pointed to the positive effects of diet on pain and the quality of life of women with endometriosis [ 22 ], which is consistent with our findings. This highlights the importance of considering nutrition in the supportive treatment of this disease. Additionally, in support of our study’s results, Szypłowska and colleagues showed that endometriosis is associated with symptoms of depression, anxiety, and impaired health-related quality of life (HR QoL). Various correlated factors affect mental health outcomes, indicating a complex relationship between this disease and patients’ mental health [ 23 ]. Huijs and Nap’s study also emphasized the role and importance of nutrition in patients with endometriosis [ 24 ]. In Krabbenborg’s study, although no specific changes in the diet were found that directly improved the quality of life of patients with endometriosis, patients felt that dietary adjustments could have a beneficial impact on disease symptoms [ 25 ]. The findings of this study underscore the necessity for age-specific therapeutic considerations. Specifically, the results indicate that progestins may be preferable for adolescents and young women due to their comparable efficacy to GnRH agonists and their fewer psychological side effects. Conversely, for adult women, OCPs could serve as maintenance therapy. These results align with recent evidence suggesting that adenomyosis often coexists with endometriosis in young patients, necessitating concurrent screening (Martire et al., 2024) [ 26 ]. Future studies should stratify outcomes by age groups to optimize personalized management. The economic burden of endometriosis treatments varies significantly across therapeutic options. A 2019 pharmacoeconomic analysis by Armour et al. [ 27 ]. A cost-benefit analysis was conducted to compare the economic viability of various hormonal contraceptives. The study found that progestins, such as dienogest, exhibited the most cost-effective profile, with an annual expense ranging from $120 to $300. This was in contrast to GnRH agonists, which required a more substantial financial investment, ranging from $1,800 to $2,500, particularly when add-back therapy was considered. OCPs also demonstrated a significant financial burden, with an annual cost ranging from $150 to $600. While GnRH agonists demonstrated a more rapid alleviation of symptoms, their elevated cost and necessity for bone-density monitoring (an increase in total expenses by 30–40%) may impede their long-term utilization, particularly in settings with limited resources. It is noteworthy that the present study’s findings on the comparative efficacy of progestins and GnRH agonists ( p  = 0.197 for QoL) suggest that progestins may offer enhanced cost-effectiveness for maintenance therapy. This is a critical consideration given the chronic nature of endometriosis [ 28 ]. Additionally, obesity has the potential to modify the responses to endometriosis treatment through metabolic pathways, such as the leptin-mediated inflammatory response. While the study revealed no substantial weight variations among the groups, the comparable efficacy of progestins to GnRH agonists suggests their potential as a weight-neutral therapy, which is consistent with the existing evidence on BMI-independent options. It is recommended that subsequent studies incorporate metabolic biomarkers to facilitate a personalized management approach [ 29 , 30 ]. The findings on treatment-emergent side effects demonstrate both consistencies and divergences from existing literature. For GnRH agonists, the onset of vasomotor symptoms that was observed in this study (4–6 weeks) is consistent with the findings reported in the trial by Taylor et al. [ 31 ] As indicated by the findings of the meta-analysis conducted by Carr et al., the onset of mood changes was observed to occur earlier in our cohort, with a median timeframe of 3–5 weeks, as opposed to the 6–8 week range reported in their study [ 32 ]. This accelerated timeline may be indicative of variations in patient demographics or dosing protocols. In the context of progestins, our groundbreaking findings on bleeding patterns were consistent with the findings of the European Progestin Study Group, as reported by Petraglia et al. [ 33 ]. The findings of this study on the side effects of OCPs (nausea, headaches, breast tenderness) are consistent with those reported by Karpowicz et al. (2024) in their Polish study, which identified common physiological symptoms. However, the population in the former study reported a higher prevalence of mood-related concerns. While early-onset symptoms were observed in the first month, the survey highlighted later-emerging psychological effects as key factors contributing to discontinuation. The observed contrast may be indicative of disparities in the study populations, specifically between endometriosis patients and general contraceptive users, as well as in the methodologies employed for monitoring, namely between clinical follow-up and self-reporting [ 34 ].

Endometriosis is a prevalent gynecological condition afflicting reproductive-aged women, typified by the presence of endometrial-like tissue extending beyond the confines of the uterus. This condition has been shown to manifest with a variety of symptoms, including, but not limited to, chronic pelvic pain, dysmenorrhea, and dyspareunia. In certain cases, it can also result in infertility [ 1 – 3 ]. Endometriosis affects physical health, mental well-being, and quality of life [ 1 ]. Given the chronic nature of symptoms and the complexity of managing the disease, the identification of effective treatments and the comparison of their impact on patients’ quality of life is imperative. Various treatment options exist for managing endometriosis, including both medical and surgical approaches [ 4 – 6 ]. Among the most commonly used medical treatments are progestins, combined oral contraceptives (OCPs), and gonadotropin-releasing hormone (GnRH) agonists. These treatments work through different mechanisms to reduce the growth of ectopic endometrial tissue and alleviate symptoms [ 7 – 12 ]. A multitude of studies have demonstrated the efficacy of these treatments in ameliorating clinical symptoms. However, the impact on various domains of quality of life exhibits variability. A body of research suggests that progestins may be effective in reducing pain and enhancing quality of life. However, ongoing debate persists regarding their long-term effects on mood and tolerability [ 13 – 16 ]. The efficacy of OCPs in regulating menstrual cycles and reducing hormonal fluctuations has been well-documented, with numerous studies highlighting their beneficial impact on quality of life and pain management. GnRH agonists, frequently administered to patients with more severe cases, have been demonstrated to be efficacious in the mitigation of pain [ 13 – 18 ] but are associated with side effects such as bone density loss and menopausal symptoms [ 7 – 12 ], This may have a deleterious effect on the quality of life in some patients. Despite these findings, there is a paucity of studies that have directly compared these three treatments within a unified framework, and the extant information is limited. This underscores the necessity for extensive research to ascertain the impact of each treatment on various domains of quality of life in women afflicted with endometriosis. The objective of this study is to compare the quality of life of patients undergoing treatment with progestins, OCPs, and GnRH agonists. The findings from this study have the potential to deepen our understanding of the impact of these treatments on the psychological, physical, and social well-being of patients, thereby providing a more informed basis for selecting the most suitable treatment option, taking into account factors such as fertility status and individual patient conditions.