Impact of oral contraceptive treatment duration on ovarian reserve markers and pain in women with ovarian endometrioma: a retrospective cohort study

This was a retrospective cohort study conducted at Okan University Hospital. Medical records of women diagnosed with ovarian endometrioma between August 2018 and August 2025 were reviewed. Patients were grouped according to whether they received oral contraceptive pill (OCP) treatment as part of routine clinical management. A total of 210 reproductive-aged women diagnosed with ovarian endometrioma were included. Ovarian endometriomas were diagnosed by transvaginal ultrasonography based on typical sonographic features, including the presence of a unilocular or multilocular ovarian cyst with homogeneous low-level internal echoes (“ground-glass” appearance), well-defined margins, and absence of papillary projections or solid components, in accordance with established criteria described by the International Ovarian Tumor Analysis (IOTA) group. Transvaginal ultrasonography was performed using a Voluson E8 ultrasound system (GE Healthcare, Zipf, Austria) equipped with a 5–9 MHz transvaginal transducer. All examinations were conducted by the same experienced radiologist to minimize inter-observer variability. In addition to the maximum cyst diameter (cm), endometrioma volume (cm³) was calculated to provide a more accurate assessment of cyst size. Volume was estimated using the prolate ellipsoid formula (length × width × height × 0.523), based on three orthogonal diameters measured during transvaginal ultrasonography. Patients were divided into two groups: Group A ( n  = 112): women with endometrioma who did not receive oral contraceptive (OCP) treatment. Group B ( n  = 98): women with endometrioma who received OCP treatment for 3–6 months. Group A ( n  = 112): women with endometrioma who did not receive oral contraceptive (OCP) treatment. Group B ( n  = 98): women with endometrioma who received OCP treatment for 3–6 months. Inclusion criteria were: (i) ovarian endometrioma diagnosed by transvaginal ultrasonography according to established IOTA criteria, (ii) age 18–40 years, and (iii) availability of baseline and follow-up data for at least 3 months. Laparoscopic confirmation was not mandatory for inclusion, and no patients underwent cystectomy prior to baseline assessment. Exclusion criteria were: (i) previous ovarian surgery, (ii) use of gonadotropin-releasing hormone (GnRH) agonists or other hormonal therapies in the past 6 months, (iii) presence of other ovarian cysts or pelvic pathologies, (iv) polycystic ovary syndrome (PCOS), and (v) systemic diseases potentially affecting ovarian reserve. Data collection was completed in August 2025. All follow-up measurements (baseline, 3 months, and 6 months) were obtained before database closure. Ethical approval was obtained in October 2025 prior to data extraction and statistical analysis. The study was conducted retrospectively using pre-existing medical records, and no additional patients were included after the database was finalized. The decision to prescribe OCPs was based on routine clinical practice, including symptom severity, fertility intentions, and anticipated waiting time for intervention. OCP treatment was primarily offered to symptomatic patients who did not plan immediate pregnancy. Patients in the non-OCP group did not receive hormonal treatment due to patient preference, contraindications to hormonal therapy, fertility considerations, or planned immediate intervention. The duration of OCP use (3 or 6 months) reflected real-world clinical practice and was determined by individual clinical circumstances rather than predefined treatment arms or random assignment. Patients in Group B received a combined oral contraceptive pill containing 30 µg ethinylestradiol and 3 mg drospirenone (Yazz ® , Bayer, Germany), administered in a continuous regimen for 3–6 months. No other oral contraceptive formulations were used during the study period. Group A did not receive any hormonal medication during follow-up. Demographic and baseline clinical data included age, body mass index (BMI), endometrioma size, serum hormone levels [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), thyroid-stimulating hormone (TSH)], and ovarian reserve markers [anti-Müllerian hormone (AMH) and antral follicle count (AFC)]. Antral follicle count (AFC) was defined as the total number of follicles measuring 2–10 mm in diameter in both ovaries and was assessed during the early follicular phase (cycle days 2–4). Serum AMH levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit, according to the manufacturer’s instructions. Other hormonal parameters were analyzed using standard automated immunoassay techniques in the hospital laboratory. Pain symptoms were evaluated using a visual analogue scale (VAS, 0–10). VAS scores reflected overall endometriosis-related pain, primarily including dysmenorrhea and chronic pelvic pain, as reported by the patients. Follow-up measurements were performed at baseline, 3 months, and 6 months. Endometrioma size was assessed by transvaginal ultrasonography, using both maximum diameter (cm) and calculated volume (cm³). For volume estimation, three perpendicular diameters were recorded at each visit, and cyst volume was calculated using the prolate ellipsoid formula. All measurements were performed by the same experienced radiologist using a standardized imaging protocol to minimize measurement bias. The primary outcomes were changes in ovarian reserve markers (AMH and AFC) associated with OCP use. Secondary outcomes included changes in endometrioma size and VAS pain scores between baseline, 3 months, and 6 months. Statistical analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). Given the retrospective design, no a priori sample size calculation was performed. Continuous variables were presented as mean ± standard deviation (SD). Normality was assessed with the Shapiro–Wilk test. Between-group comparisons were performed using the independent-samples t-test or Mann–Whitney U test, as appropriate. Categorical variables were compared using chi-square or Fisher’s exact test. Within-group comparisons (baseline vs. 3 months vs. 6 months) were evaluated using paired t-test or Wilcoxon signed-rank test. A p-value < 0.05 was considered statistically significant. Missing data were minimal and handled by complete-case analysis. This study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was reviewed and approved by the Clinical Research Ethics Committee of Medipol University (Approval No: [E-10840098-202.3.02-6780], Date: [02.10.2025]). As this was a retrospective study based on patient records, the requirement for informed consent was waived by the ethics committee. This study has been reported in accordance with the STROBE guidelines. The completed STROBE checklist has been provided as a supplementary file.

A total of 210 women with ovarian endometrioma were included in the study: 112 in Group A (no OCP treatment) and 98 in Group B (OCP treatment). The baseline demographic and clinical characteristics of the two groups are summarized in Table  1 . Table 1 Baseline demographic and clinical characteristics Variable Group A (No OCP) ( n  = 112) Group B (OCP) ( n  = 98) p -value Age (years) 31.22 ± 3.73 30.75 ± 3.82 0.146 BMI (kg/m²) 26.32 ± 4.07 25.69 ± 3.04 0.256 Endometrioma size (cm) 4.52 ± 1.78 4.71 ± 1.89 0.434 Endometrioma volume (cm³) 76.26 ± 7.21 84.11 ± 7.93 0.204 AMH (ng/mL) 2.87 ± 1.02 2.56 ± 0.98 0.094 AFC (n) 11.2 ± 4.4 10.9 ± 4.1 0.412 VAS pain score 5.8 ± 2.4 8.3 ± 3.4 0.106 FSH (IU/L) 6.4 ± 2.1 7.1 ± 2.9 0.036 LH (IU/L) 3.5 ± 2.2 3.7 ± 2.1 0.203 Estradiol (pg/mL) 31.2 ± 21.2 34.0 ± 23.4 0.268 TSH (mIU/L) 2.34 ± 0.67 2.89 ± 0.73 0.298 Data are presented as mean ± standard deviation Abbreviations : AMH Anti-Müllerian hormone, AFC Antral follicle count, BMI Body mass index, VAS Visual analogue scale, FSH Follicle-stimulating hormone, LH Luteinizing hormone, TSH Thyroid-stimulating hormone Baseline demographic and clinical characteristics Data are presented as mean ± standard deviation Abbreviations : AMH Anti-Müllerian hormone, AFC Antral follicle count, BMI Body mass index, VAS Visual analogue scale, FSH Follicle-stimulating hormone, LH Luteinizing hormone, TSH Thyroid-stimulating hormone There were no significant differences between the groups regarding age, BMI, endometrioma size, AMH, AFC, LH, estradiol, or TSH levels (all p  > 0.05) However, mean VAS pain scores tended to be higher in Group B than in Group A, although the difference did not reach statistical significance (VAS: 8.3 ± 3.4 vs. 5.8 ± 2.4, p  = 0.106). In contrast, baseline FSH levels were slightly higher in Group B (7.1 ± 2.9 vs. 6.4 ± 2.1, p  = 0.036) (Table  1 ). At the 3-month follow-up, Group B demonstrated a significant reduction in VAS pain scores compared with Group A (3.8 ± 1.4 vs. 6.2 ± 2.7, p  = 0.032. When assessed by cyst volume, OCP-treated patients demonstrated a significantly lower mean endometrioma volume compared with untreated patients at 3 months (56.64 ± 4.92 vs. 96.28 ± 9.66 cm³, p  = 0.041), suggesting that volume may capture treatment-related change more sensitively than diameter. Ovarian reserve markers were significantly lower in Group B compared with Group A at 3 months: AMH (1.96 ± 0.76 vs. 2.66 ± 0.92 ng/mL, p  = 0.043) and AFC (7.2 ± 3.3 vs. 10.2 ± 4.2, p  = 0.022) (Table  2 ). Table 2 Comparison of clinical and ovarian reserve outcomes at 3 months Variable Group A (No OCP) ( n  = 112) Group B (OCP) ( n  = 98) p -value Endometrioma diameter (cm) 4.92 ± 1.89 4.01 ± 1.56 0.102 Endometrioma volume (cm³) 96.28 ± 9.66 56.64 ± 4.92 0.041 VAS pain score 6.2 ± 2.7 3.8 ± 1.4 0.032 AMH (ng/mL) 2.66 ± 0.92 1.96 ± 0.76 0.043 AFC (n) 10.2 ± 4.2 7.2 ± 3.3 0.022 Data are presented as mean ± standard deviation Abbreviations : VAS Visual analogue scale, AMH Anti-Müllerian hormone, AFC Antral follicle count Comparison of clinical and ovarian reserve outcomes at 3 months Data are presented as mean ± standard deviation Abbreviations : VAS Visual analogue scale, AMH Anti-Müllerian hormone, AFC Antral follicle count At the 6-month follow-up, OCP-treated patients (Group B) showed a significant decrease in endometrioma size compared with untreated patients (3.91 ± 1.56 vs. 5.12 ± 1.97 cm, p  = 0.048). At 6 months, mean endometrioma volume was also significantly lower in the OCP group compared with the non-OCP group (45.32 ± 5.41 vs. 127.74 ± 11.62 cm³, p  = 0.008). VAS pain scores remained significantly lower in Group B (3.6 ± 1.1 vs. 6.4 ± 2.9, p  = 0.012). At 6 months, ovarian reserve markers remained significantly lower in Group B compared with Group A. Mean AMH levels were significantly lower (1.76 ± 0.88 vs. 2.64 ± 0.87 ng/mL, p  = 0.021), as were AFC values (6.1 ± 2.1 vs. 9.8 ± 3.1, p  = 0.011) (Table  3 ). Table 3 Outcomes at 6 months and within-group changes in OCP users Variable Group A (No OCP) Group B (OCP) p (A vs. B, 6 mo) Group B (3 mo) Group B (6 mo) p (3 vs. 6 mo) Endometrioma diameter (cm) 5.12 ± 1.97 3.91 ± 1.56 0.048 4.01 ± 1.56 3.91 ± 1.56 0.688 Endometrioma volume (cm³) 127.74 ± 11.62 45.32 ± 5.41 0.008 56.64 ± 4.92 45.32 ± 5.41 0.188 VAS pain score 6.4 ± 2.9 3.6 ± 1.1 0.012 3.8 ± 1.4 3.6 ± 1.1 0.702 AMH (ng/mL) 2.64 ± 0.87 1.76 ± 0.88 0.021 1.96 ± 0.76 1.76 ± 0.88 0.221 AFC (n) 9.8 ± 3.1 6.1 ± 2.1 0.011 7.2 ± 3.3 6.1 ± 2.1 0.204 Data are presented as mean ± standard deviation Abbreviations : Visual analogue scale, AMH Anti-Müllerian hormone, AFC Antral follicle count Outcomes at 6 months and within-group changes in OCP users Data are presented as mean ± standard deviation Abbreviations : Visual analogue scale, AMH Anti-Müllerian hormone, AFC Antral follicle count Within Group B, there were no significant differences between the 3- and 6-month follow-ups for any parameter. Both endometrioma diameter (4.01 ± 1.56 vs. 3.91 ± 1.56 cm, p  = 0.688) and cyst volume (56.64 ± 4.92 vs. 45.32 ± 5.41 cm³, p  = 0.188) remained stable between the two time points. Likewise, VAS pain scores (3.8 ± 1.4 vs. 3.6 ± 1.1, p  = 0.702), AMH levels (1.96 ± 0.76 vs. 1.76 ± 0.88 ng/mL, p  = 0.221), and AFC values (7.2 ± 3.3 vs. 6.1 ± 2.1, p  = 0.204) did not demonstrate further significant changes (Table  3 ).

In women with ovarian endometrioma, oral contraceptive use was associated with improvements in pain and cyst size, accompanied by lower ovarian reserve marker levels during treatment, likely reflecting pharmacologic suppression. No additional benefits were observed with treatment beyond three months, highlighting the importance of individualized treatment duration, particularly in women planning future fertility.

In this retrospective cohort study, we observed that oral contraceptive (OCP) use in women with ovarian endometriomas was associated with improvements in pain scores and cyst size. However, these findings were accompanied by lower ovarian reserve marker levels, as reflected by AMH and AFC values. The reduction in ovarian reserve marker levels was observed within the first three months of treatment and did not change further with continued OCP use. Our findings are in line with prior studies demonstrating that oral contraceptives (OCPs) are highly effective for endometriosis-associated pain relief and for reducing the risk of cyst recurrence [ 6 – 8 ]. In the current cohort, pain scores improved markedly after three months of treatment and remained low at six months, indicating that short-term OCP use is a reliable option for symptomatic control. Similarly, endometrioma size was significantly reduced by six months, consistent with previous reports showing that hormonal suppression can limit cyst progression [ 10 ]. The observed association between OCP use and lower ovarian reserve marker levels highlights an important clinical dilemma. Several studies and meta-analyses have demonstrated that women with ovarian endometriomas already exhibit lower serum AMH levels compared with healthy controls [ 11 , 12 ]. In addition, hormonal contraceptives have been shown to reduce AMH and AFC, most likely through suppression of gonadotropin-dependent follicular growth rather than irreversible follicular loss [ 13 , 14 ]. A recent systematic review suggested that AMH levels often decline during OCP use but may recover after discontinuation, although the duration of suppression and the extent of reversibility remain subjects of debate [ 15 ]. Accordingly, AMH and AFC values obtained during active OCP use should be interpreted as markers of ovarian activity under pharmacologic suppression rather than definitive indicators of long-term fertility potential [ 13 , 15 ]. In the absence of post-discontinuation measurements, our study cannot determine whether the observed reductions represent temporary suppression or sustained changes in ovarian reserve. Although baseline FSH levels were statistically higher in the OCP group, both values were within normal reproductive limits. Basal FSH is known to demonstrate considerable inter-cycle variability and is generally considered a relatively late marker of ovarian reserve decline. In contrast, AMH and AFC are regarded as more sensitive and stable indicators of the growing follicular pool [ 14 , 16 ]. Importantly, baseline AMH and AFC levels did not differ significantly between the groups, suggesting comparable ovarian reserve status at study entry. Our results add to this growing body of evidence by showing that AMH and AFC levels declined significantly after three months of OCP treatment, with no further reduction observed at six months. The lack of further change after three months suggests that the initial reduction may reflect hormonal suppression rather than progressive depletion of ovarian reserve. In this context, decreased AMH levels during active treatment should be interpreted as an expected biological consequence of gonadotropin suppression and reduced follicular recruitment rather than direct follicular depletion [ 13 ]. Previous studies have demonstrated lower AMH levels in hormonal contraceptive users and partial recovery after discontinuation [ 15 ]. Accordingly, reduced ovarian reserve markers during OCP use do not necessarily indicate diminished long-term fertility potential. In the absence of post-discontinuation measurements, our study cannot determine whether the observed reductions represent temporary suppression or sustained changes in ovarian reserve. From a clinical standpoint, AMH measurement during active OCP therapy should not be used to estimate reproductive prognosis, as these markers reflect ovarian functional activity under hormonal suppression rather than true ovarian reserve [ 13 , 15 ]. Current ESHRE guidelines emphasize symptom control as the primary goal of hormonal therapy in endometriosis management rather than fertility prediction during active treatment [ 9 ]. Importantly, no additional clinical benefits in terms of pain relief or cyst size reduction were observed beyond the third month of treatment, underscoring the limited incremental value of extending OCP therapy beyond three months in this cohort. These findings emphasize the importance of individualized management strategies. For women primarily seeking symptom relief or those postponing fertility treatment, short-term OCP therapy may provide substantial benefit with acceptable risk. Conversely, for patients actively planning pregnancy, even temporary reductions in AMH and AFC may influence reproductive decision-making, including the consideration of fertility preservation options. This balance between effective symptom control and preservation of reproductive potential has been increasingly highlighted in recent guidelines and expert consensus statements [ 16 , 17 ]. The strengths of this study include its relatively large sample size, the combined assessment of biological and clinical outcomes, and the longitudinal follow-up over a six-month period. Nevertheless, several limitations should be acknowledged. The retrospective design and single-center setting may limit generalizability and introduce selection bias; however, the use of standardized imaging protocols and consistent follow-up intervals strengthens the internal validity of the findings. In addition, slightly higher baseline FSH levels in the OCP group may reflect non-random treatment allocation inherent to real-world clinical practice, although baseline AMH and AFC levels were comparable between groups. The lack of post-discontinuation follow-up precludes evaluation of potential recovery of ovarian reserve markers. Therefore irreversible depletion of ovarian reserve cannot be inferred, and the observed reductions in AMH and AFC may reflect functional suppression during active OCP treatment. Suppression of serum AMH during OCP use may also underestimate true ovarian reserve, which is particularly relevant for women planning pregnancy. Furthermore, surgical confirmation of endometrioma was not systematically performed, as patients were managed conservatively to avoid potential surgery-related decline in ovarian reserve markers such as AMH. Although diagnosis was based on standardized IOTA ultrasonographic criteria performed by an experienced radiologist, the absence of histopathological confirmation may represent a limitation of the study. Future prospective, randomized studies with long-term and post-treatment follow-up are needed to clarify the reversibility of OCP-induced changes in AMH and AFC and to guide fertility-focused counseling and individualized treatment strategies.

Endometriosis is a chronic, estrogen-dependent condition that affects approximately 10–15% of reproductive-aged women and is strongly associated with infertility and chronic pelvic pain [ 1 , 2 ]. Among its phenotypes, ovarian endometriomas are observed in up to 44% of patients and may compromise ovarian function through both mechanical disruption and inflammatory mechanisms within the ovarian cortex [ 3 ]. Ovarian reserve, typically evaluated by anti-Müllerian hormone (AMH) levels and antral follicle count (AFC), is often diminished in women with endometriomas. Several prospective studies have shown accelerated decline of ovarian reserve in this population, even without prior surgical intervention [ 4 , 5 ]. This reduction has important implications for fertility preservation and reproductive planning. Medical therapy is frequently offered to control pain and suppress progression. Combined oral contraceptive pills (OCPs) are widely prescribed for endometriosis-related symptoms and have been shown to reduce dysmenorrhea and are commonly used in the long-term management of endometriosis-related symptoms, including after surgery [ 6 , 7 ]. Their role in preventing endometrioma growth and alleviating pelvic pain has been well established [ 8 ]. Current guidelines from the European Society of Human Reproduction and Embryology (ESHRE) recommend OCPs as a first-line option for long-term management of endometriosis-associated pain [ 9 ]. Nevertheless, the effect of OCPs on ovarian reserve remains uncertain. While symptom control is a consistent benefit, concerns persist regarding whether prolonged suppression might negatively influence AMH and AFC. Clarifying this balance between clinical efficacy and potential compromise of ovarian reserve is crucial, especially in women desiring future fertility. In routine clinical practice, the optimal duration of OCP use in women with ovarian endometrioma—particularly with regard to balancing symptom control and preservation of ovarian reserve—remains unclear. Therefore, in this study, we aimed to evaluate the association between OCP treatment duration and ovarian reserve markers (AMH and AFC), endometrioma size, and pain scores in women with ovarian endometrioma by comparing outcomes at baseline, 3 months, and 6 months.