Figures
Abstract
Objective
This exploratory analysis of a randomized controlled trial aimed to identify baseline predictors of dropout in overweight women with polycystic ovary syndrome (PCOS) participating in a lifestyle intervention program.
Methods
An exploratory analysis was conducted using data from a randomized controlled trial involving overweight or insulin-resistant women with PCOS aged 18–45. All participants received cyclic progestin, metformin, and a structured lifestyle intervention. Dropout was defined as proactive withdrawal, missing two consecutive visits, or loss of contact for more than six months. Univariate and adjusted multivariable logistic regression models were used to identify factors associated with dropout.
Results
Among the participants, 61.06% (n = 69) dropped out within one year. No significant differences were observed in baseline demographic, clinical, biochemical, psychological, or dietary characteristics between completers and dropouts. However, baseline physical activity level (PAL), objectively measured using an accelerometer, was identified as the strongest predictor of dropout. Each 0.3-unit increase in PAL was associated with a 29.6% reduction in the likelihood of dropout.
Citation: Xie M, Zhou S, Wu J, Luo X, Guo Y, Qiao L, et al. (2026) Determinants of dropout from lifestyle interventions for overweight polycystic ovary syndrome: An exploratory analysis of randomized controlled trial. PLoS One 21(6): e0351575. https://doi.org/10.1371/journal.pone.0351575
Editor: Wan-Xi Yang, Zhejiang University College of Life Sciences, CHINA
Received: December 2, 2025; Accepted: May 23, 2026; Published: June 26, 2026
Copyright: © 2026 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data supporting the findings of this study are provided within the paper and its Supporting Information files (S2 File. Dataset). The minimal data set underlying the reported results has been included as a fully anonymized dataset in the Supporting Information. No additional data needs to be requested from the corresponding author.
Funding: Study is supported by the Bethune Foundation’s 2020 Young and Middle-Aged Physicians Excellence Training Program-Women’s Health Research Project (Grant No. 20H0604), the Sichuan Key Research & Development Project (2021YFS0127), and the Chengdu Technological Innovation Research and Development Project (2024-YF05-00258-SN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Polycystic ovary syndrome (PCOS) is a prevalent and heterogeneous endocrine disorder affects 8% to 13% of reproductive-aged women globally, characterised by a constellation of interrelated reproductive abnormalities. Diagnosis is base on the presence of irregular menstrual cycles and/or hyperandrogenism, alongside either ultrasound evidence of polycystic ovarian morphology or elevated anti-müllerian hormone levels [1]. Additionally, PCOS is associated with the development of metabolic syndrome in up to 33% of affected women [2]. These combined reproductive and metabolic disturbances elevate the risk of major health complications over the lifespan, such as anovulatory infertility and type 2 diabetes [3], resulting in significant health and economic consequences.
While various theories have been proposed to elucidate the pathogenesis of PCOS, obesity emerges as a key pathophysiological component. Approximately 50% to 80% of women with PCOS are concurrently obese [4]. Moreover, evidence from Mendelian randomization analyses suggests a causal relationship between body mass index (BMI) and PCOS [5–7]. Obesity contributes to PCOS development through multiple mechanisms. For instance, the severity of obesity correlates with the extent of selective insulin resistance (IR). IR, along with consequent hyperinsulinemia, activates excessive ovarian androgen production, thereby accelerating PCOS development [8]. Additionally, obesity-related inflammation may exert potential effects on ovarian physiology due to dysregulated adipokine secretion, further impacting insulin sensitivity [9]. Collectively, it is well established that obesity exacerbates PCOS manifestations, while weight loss ameliorates the features of PCOS.
According to the international evidence-based guideline, first-line treatments for women with PCOS are lifestyle interventions, comprising dietary modification, exercise, and behavioural strategies [1]. Emphasis on prevention of weight gain and regular weight monitoring is crucial in PCOS management. Notably, achieving a targeted weight reduction of 5% to 10% demonstrated benefits in improving both reproductive and metabolic function indicators in women with PCOS [10]. However, existing clinical trials investigating the impact of weight loss in women with PCOS predominantly feature short to medium follow-up durations ranging from 4 weeks to 6 months, involving small sample sizes of 12–100 participants [11]. Despite effort to enhance adherence through more frequent visits in the intervention group, the rigorous lifestyle interventions employed, such as strict calorie restriction, often prove physiologically unrealistic and unsustainable [10]. Consequently, even in short-term follow-ups, considerable dropout rates are reported, potentially exaggerating treatment effects [11]. Furthermore, several medium- to long-term trials with follow-ups of at least 6 months reported dropout rates of 31% to 63% over six months, with a significant proportion of participants quitting the trial within the first 8 weeks [12–14]. It becomes evident that a single lifestyle prescription is unlikely to provide effective long-term management solutions.
Subsequently, growing attention has been directed toward maintaining adherence among women with PCOS undergoing lifestyle interventions and reducing high dropout rates in weight management. Identifying baseline characteristics linked with dropout is crucial for recognising individuals who could benefit from such interventions or who require alternative supports to achieve weight loss goals. While lower quality of life (QoL) score, higher baseline weight, elevated androstenedione level, elevated free and total testosterone level, and increased depressions score at baseline have been linked to higher dropout rates in prior studies [12–14], few investigations have explored dietary preferences, physical activity level (PAL), and body composition as predictors in overweight women with PCOS. Notably, these factors are robust predictors of weight loss maintenance in the general population, as supported by a systematic review [15]. The same review highlighted inconclusive value of depression scores and QoL due to the limited study numbers, warranting further investigation [15].
This exploratory analysis, conducted within a randomized controlled trial, aims to identify potential baseline characteristics associated with dropout during the lifestyle interventions in overweight women with PCOS. Baseline factors encompass menstrual characteristics, PCOS features, biochemical parameters, psychological scores, dietary and physical activity questionnaires, and objectively measured body composition, and exercise capacity.
Materials and methods
Study design and setting
This exploratory analysis used data from a randomized controlled trial (RCT) conducted at the PCOS clinic within the Department of Reproductive Endocrinology, West China Second University Hospital, China. The primary aim of RCT was to compare the efficacy of a network platform-based lifestyle intervention combined with medication against standard care in improving reproductive function among women with PCOS.
Ethics statement
The study was approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Approval No. 2020(060)) and registered with the Chinese Clinical Trial Registry (ChiCTR2000034263) on June 20, 2020. All procedures adhered to the Declaration of Helsinki. Written informed consent was obtained from all participants prior to enrolment.
Participants
Eligible women were recruited between September 20, 2020, and December 30, 2022. Inclusion criteria were: age 18–45 years; PCOS diagnosis per Rotterdam 2003 criteria; BMI > 23.9 kg/m² or HOMA-defined insulin resistance; no pregnancy intention within the next year; smartphone proficiency; and willingness to adjust lifestyle. Exclusion criteria included: conditions contraindicating dietary protein or exercise (e.g., chronic kidney disease, heart failure, severe joint or gastrointestinal disease); psychological disorders; malignant tumors; recent weight-loss medication/surgery (within 3 months); use of drugs affecting hormone or glucolipid metabolism; allergy to dydrogesterone or metformin; participation in other trials within the past month; and abnormal cervical cytology (excluding inflammatory lesions). The sample size calculation was based on a notable difference in ovulation rate as the primary outcome measure of this RCT. A total of 114 participants (57 per group) were enrolled, a number lower than the planned 130 (65 per group, accounting for a 10% dropout) due to recruitment challenges. Randomization(1:1 ratio) using a computer-generated random table, performed by a research doctor not involved in the study.
Baseline Characteristics Measurements
The baseline characteristics included the following domains:
- Gynaecological factors: Menarche age, menstrual patterns (duration and cycle length), dysmenorrhea, gravidity, and parity (self-report/medical records).
- Anthropometry and body composition: Systolic/diastolic blood pressure, BMI, Waist-to-hip ratio (WHR). The Mobility Evaluation System (MES) (software version Mes-01S20, MaiDaKang, Beijing, China) assessed body fat percentage (BF%), strength of the lower limbs (SLL), range of motion (ROM), and PAL.
- PCOS characteristics: Clinical signs (Ferriman–Gallwey score, acne, baldness, acanthosis nigricans) were evaluated by specialists. Biochemical assays included insulin-related parameters (fasting, 1-hour, and 2-hour postprandial insulin; HOMA-IR(calculated as FINS×FPG/22.5)), glucose levels (fasting, 1-hour, and 2-hour postprandial glucose), lipid profile (total cholesterol and triglycerides), and reproductive hormones (estradiol, LH/FSH ratio, free androgen index, androstenedione, DHEAS, and SHBG). Sex hormone measurements were taken on days 2–5 of the menstrual cycle or during amenorrhea, other blood tests were cycle-phase independent.
- Lifestyle characteristics: Baseline psychological distress was assessed using the Huaxi Emotional-Distress Index (HEI), a validated scale for assessing depression and anxiety among Chinese patients [16,17]. PCOS-specific quality of life was measured using the PCOS Health-Related Quality of Life Questionnaire (Chi-PCOSQ) [18]. Physical activity was evaluated using the long-form International Physical Activity Questionnaire (IPAQ) [19], and dietary habits using a revised version of the Semiquantitative Food Frequency Questionnaire (SQFFQ) [20]. All instruments have demonstrated satisfactory reliability and validity in previous studies.
Interventions
All participants received standardized medication: cyclic dydrogesterone(20 mg/day for 14 days in the last half of the menstrual cycle) and metformin (1500 mg/day). In addition, they received structured lifestyle guidance, including dietary and physical activity guidance from a nutritionist. Participants were randomly allocated into one of two groups. The first group was invited to use a network interactive platform for self‐monitored and receiving monthly reminders; transmission was not mandatory. The second group received medication treatment and lifestyle modification without the platform or reminders.
Outcomes
women with PCOS were advised to attend clinic every three months for weight assessment and prescriptions renewal. Dropout was defined as proactive withdrawal, missing two consecutive return visits, or loss of contact for over six months.
Statistical analysis
Potential predictors were preselected based on the literature. Logistic regression was used to identify dropout-associated variables. A univariate analysis retained variables with p < 0.10. Multicollinearity among selected variables was examined using a correlation matrix; for highly correlated pairs (r > 0.80), the variable with greater clinical relevance and univariate significance was retained. A backward stepwise logistic regression was then performed, removing non-significant predictors (p > 0.05). The final model was assessed for goodness-of-fit using the Hosmer-Lemeshow test. Multicollinearity was further evaluated using tolerance and variance inflation factor (VIF). Model explanatory power was quantified by Nagelkerke's pseudo R², and discriminative ability by the area under the receiver operating characteristic (ROC) curve.
Results
Baseline characteristics of women with PCOS
A total of sixty-nine women (61.06%) dropped out of the lifestyle interventions (Fig 1), with no significant differences in attrition rates observed between the network interactive platform group and the control group (p = 0.444). Key baseline comparisons between dropouts and completers (Table 1) showed that dropouts had significantly lower PAL (1.42 vs. 1.50, p = 0.002) and higher BMI (27.99 vs. 26.35 kg/m², p = 0.028), as well as a higher prevalence of acanthosis nigricans (38.2% vs. 15.9%, p = 0.019). Trends toward higher gravidity, weight, and body fat percentage were observed in dropouts (p = 0.056–0.076). No significant differences were observed in psychological measures or most dietary factors. Except for lower vitamin C intake in the dropout group (p = 0.044), no other dietary differences were detected.
Unadjusted univariable logistic regression and correlation between predictive factors
Univariate analysis identified BMI, body fat percentage, weight, and PAL as associated with dropout (p < 0.10). Due to strong collinearity among adiposity indicators (pairwise Pearson correlations: weight vs. BMI = 0.89, weight vs. body fat percentage = 0.92, BMI vs. body fat percentage = 0.94), only BMI, which showed the strongest univariate association and a more readily interpretable effect size, was retained for the multivariable analysis (Tables 2 and 3).
Adjusted multivariable logistic regression on predictive factors
Multivariable logistic regression identified baseline PAL as the sole independent predictor of dropout after adjusting for other factors (Table 4). Each unit increase in PAL corresponded to a 98.5% lower likelihood of dropout (OR = 0.015, 95% CI: 0.001–0.352), equivalent to a 29.6% reduction per 0.3-unit increase. The model explained 19.5% of the variance (Nagelkerke R² = 0.195) and showed acceptable discrimination (AUC = 0.705, 95% CI: 0.605–0.804), with no evidence of miscalibration (Hosmer–Lemeshow p = 0.847) or multicollinearity (all VIF < 4)(Fig 2). Categorical analysis by PAL level was precluded due to the small number of participants in higher activity categories (n = 4 in dropouts, n = 5 in completers).
Discussion
This study identified baseline objectively measured PAL as the sole and strongest predictor of dropout among overweight women with PCOS undergoing lifestyle interventions. Contrary to our expectations, the network interactive platform did not improve adherence or reduce dropout rates. Notably, none of the previously reported predictors (psychological factors, androgen levels, quality of life) were replicated, underscoring the unique role of PAL in this population.
PAL is a dimensionless index reflecting total energy expenditure relative to basal metabolic rate (BMR) over 24 hours [21]. It is calculated as total energy expenditure (TEE) divided by BMR. Notably, BMR accounts for the largest component of TEE. While higher activity-induced energy expenditure(AEE) would intuitively lead to a higher PAL, overweight and obese individuals do not necessarily have lower PAL. In fact, their AEE may be similar or even higher than that of leaner individuals [22]. This apparent paradox occurs because BMR is largely determined by body size—heavier individuals expend more energy on fundamental metabolic functions (e.g., breathing, ion transport, enzyme turnover) [22].
The predictive value of PAL extends beyond PCOS. Lower objectively measured PAL is a strong predictor of all--cause mortality in chronic obstructive pulmonary disease [23], and higher PAL predicts successful long-term weight loss (2–5 years) in the general population [24,25]. However, evidence in endocrine disorders, particularly PCOS, remains limited. Of note, although we measured PAL both objectively (accelerometers) and subjectively (self-report), only the objective measure was associated with dropout. This discrepancy likely reflects common overestimation of physical activity in self-report, highlighting the need for accelerometer-based measures in clinical practice [26].
Unlike previous studies that identified psychological or biochemical predictors of dropout in women with PCOS, our findings revealed no such associations. Regarding psychological factors, our participants reported higher baseline PCOSQ scores than those in other studies using the Chi-PCOSQ [27], suggesting fewer PCOS-related negative moods and, consequently, smaller emotional differences between dropouts and completers. Regarding biochemical factors, we observed no significant differences in androgen levels between the two groups. This may be explained by ethnic variations in PCOS phenotypes: Western populations tend to present with more pronounced hyperandrogenism and hirsutism [12,13], whereas Asian women with PCOS more commonly exhibit metabolic syndrome and its related features [28]. In line with this, our participants had relatively low Ferriman Gallwey scores, further accounting for the divergence between our results and those of earlier investigations.
This study have several notable strengths. First, we assessed a comprehensive set of baseline predictors, including lifestyle characteristics often overlooked previously. This allowed us to adjust for confounders and identify objectively measured PAL, rather than baseline weight [12], as the sole dropout predictor. Second, this exploratory analysis stemmed from a randomized controlled trial, with strict inclusion criteria and standardised treatment protocols, ensured a homogeneous participant background and consistent measurements, strengthening causal inference.
A notable consideration is the high discontinuation rate observed in both the intervention and control groups, which is consistent with previous PCOS lifestyle trials [11]. Contrary to our expectations, the network interactive platform did not improve adherence or reduce dropout rates, despite a prior RCT reporting such benefits [29]. This lack of effect may be explained by habituation, whereby monthly reminders were perceived as intrusive and lost their effectiveness over time [30]. Moreover, unlike previous studies has using one-way text message reminders, our platform required mutual communication: participants had to regularly report their diet and physical activity. The time burden and stress associated with reporting unfulfilled monthly goals may have further undermined adherence. Therefore, alternative support strategies are needed. Future research should explore less intrusive reminder methods and optimal frequency thresholds to facilitate effective collaboration between providers and patients undergoing long-term lifestyle interventions.
Another consideration is the distribution of PAL categories in our sample. According to the 2004 FAO/WHO/UNU classification, PAL values of 1.40–1.69, 1.70–1.99, and 2.00–2.40 correspond to sedentary/light active, moderately active, and vigorous/very active lifestyles, respectively. Owing to the limited number of participants with higher PAL levels, we could not perform categorical analyses. Nevertheless, our continuous analysis clearly demonstrates that each 0.3-unit increase in PAL reduces dropout likelihood by approximately 30%. These findings underscores the value of objective PAL measurement over self-reported questionnaires, enabling the identification of at-risk individuals who may require additional support to improve long-term adherence.
Finally, as this is an exploratory analysis with a relatively small sample size and multiple variables examined, the p-values reported should be interpreted with caution. The hypothesis-generating nature of our study means that the observed associations, while promising, require confirmation in larger, well‑powered prospective studies. Readers are advised to view the statistical findings as supportive evidence rather than definitive conclusions.
Conclusions
In conclusion, unlike previous studies, we identified baseline objectively measured PAL as the sole and strongest predictor of dropout in overweight women with PCOS undergoing lifestyle interventions. This finding highlights that higher PAL, assessed objectively, is associated with better treatment adherence. Clinically, we recommend routine objective screening for PAL in women with PCOS. Those with lower PAL should receive additional support alongside lifestyle interventions to improve adherence and promote weight loss.
Acknowledgments
The authors thank all researchers and participants. The authors confirm that all ongoing and related trials for this intervention are registered. The study design has been registered and described in the Chinese Clinical Trial Registry (ChiCTR2000034263) as of June 20, 2020.
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