The feasibility of progressive resistance training in women with polycystic ovary syndrome: a pilot randomized controlled trial

Polycystic ovary syndrome (PCOS) is a common endocrine disease that affects 9-18 % of women [1]. Hyperandrogenism, menstrual irregularity and polycystic ovaries define the condition [2], and common features include insulin resistance, hirsutism, acne, alopecia, and markers of cardiometabolic disease risk (e.g. android obesity, inflammation, dyslipidemia, etc.) [3, 4]. PCOS is a leading cause of oligo/anovulation and oligo/amenorrhea, infertility, and miscarriages [5, 6]. Depression [7], anxiety [8], body image difficulties [9] and low health-related quality of life (HRQoL) [10] are common in this population.

Clinical trials in PCOS have shown that aerobic training (e.g. cycling, walking) or high-intensity interval training prescribed for 12-24 weeks can significantly improve important clinical outcomes, including insulin sensitivity, body fat percentage, total and LDL-cholesterol, c-reactive protein (CRP), and psychological outcomes (e.g. HRQoL and depression) [11‐17]. Such studies have informed clinical practice guidelines, which recommend that women with PCOS engage in ≥90 min of aerobic training weekly [18].

Progressive resistance training (PRT) is the most potent exercise modality for improving skeletal muscle mass and quality [19, 20]. Notably, studies have consistently shown that PRT can counteract metabolic diseases, including insulin resistance [20‐23]. This is a key consideration for women with PCOS given that insulin resistance is implicated in the etiology of the disease [24]. The myogenic adaptations induced by PRT are often accompanied by a range of physiological (metabolic), functional and psychological adaptations that may be clinically important in this cohort [19]. PRT is currently recommended within exercise prescription guidelines for healthy adults and those with other major chronic diseases, including type 2 diabetes [25‐31]. However, PRT is not currently recommended within clinical practice guidelines for PCOS [18].

Only two studies to date have investigated the isolated effect of PRT in women with PCOS [32‐34]. These studies have shown that chronic PRT (10-16 weeks) can significantly improve several clinically important outcomes in this cohort, including body composition, circulating androgens, blood glucose, sexual dysfunction, depression and anxiety [32‐34]. However, there is currently a need for additional research on the safety and efficacy of PRT in PCOS utilizing robust study designs. Therefore, the purpose of the present pilot study was to evaluate the feasibility of a executing a randomized controlled trial (RCT) of PRT in women with PCOS to inform the development of a large-scale clinical trial.

This pilot study evaluated the feasibility of a PRT intervention in women with PCOS within an RCT to inform the development of a robust clinical trial. Our findings suggest that it is feasible to investigate PRT in women with PCOS, and that this anabolic intervention may induce a number of clinically important adaptations.

The study enrolled approximately two participants per month over 7.5 months. This rate of recruitment is similar to studies prescribing aerobic training in women with PCOS (0.5 to 3 women per month) [45‐49]. However, the duration of recruitment in these studies was longer (8-40 months) resulting in larger sample sizes (n = 20 to n = 124) [45‐49]. Other studies have not stated the duration of recruitment [14‐16, 50‐52]. Clearly, participant recruitment is a challenging aspect of clinical research [53], and strategies for enhancing recruitment are therefore important. Our most successful recruitment methods were the social media platform Facebook (n = 6, 40 %) and online advertisement via Gumtree (n = 4, 26.6 %). The least successful strategies included referral by local clinicians (n = 3, 20 %), research colleagues (n = 1, 6.7 %) and flyers (n = 1, 6.7 %). Having the support of local clinicians is essential to fostering participant recruitment in clinical trials [54]. However, clinicians are often busy with their own professional duties and may not be able to offer the level of support required [55]. To foster recruitment via clinicians, it may be necessary to engage in regular meetings and/or create more streamlined pathways for referral.

Although Facebook was our most effective recruitment method, it also resulted in a large number of ineligible women contacting the principal investigator. Future studies conducted within small geographic regions should consider more targeted methods of advertising via Facebook (i.e. paid advertisement to more effectively reach the local community). Alternatively, studies conducted across multiple geographical sites or countries may benefit from using Facebook for wider-scale recruitment. No previous study of exercise in PCOS has noted the use of Facebook as a recruitment method [14, 16, 45, 48‐51].

Our participant attrition rate was 38 % overall (i.e. 29 % (2/7) in the PRT group and 50 % (3/6) in the control group). Previous studies of exercise training in PCOS have reported participant attrition rates ranging from 25 % to 45 % [14, 45, 47‐49, 51], while other studies have not provided these data [46, 48, 52]. In the present study, two women in the control group were lost immediately after randomization, while three other women consented and withdrew from the study given their concerns about randomization. It has been suggested that participants who are randomized to a no-treatment control group, or a treatment group contrary to their desire, may not accept randomization and refuse participation [56]. Strategies to minimize participant attrition may include the use of a placebo-control (i.e. unloaded or non-progressive training) or a waitlist control group. Moreover, future studies could opt to investigate the additive effect of PRT to an exercise intervention prescribed according to current guidelines which emphasize aerobic training [17, 18], i.e. by comparing a group receiving PRT plus aerobic training to a group receiving aerobic training only.

Attendance to supervised training sessions in the present study was high (95 ± 6 %). High attendance rates to supervised training (>80 %) have been noted in many trials of aerobic training in PCOS [16, 46, 52]. By comparison, attendance to the home-based sessions in the present study was lower (51 %). A previous PCOS study which prescribed unsupervised exercise (i.e. walking) also demonstrated a lower compliance rate (43 %) [48]. Studies in other cohorts have reported both high [57] and low compliance to home-based training [58]. Potential reasons for low compliance to home-based exercise prescriptions may include lack of motivation or time [59]. Future studies should consider possible strategies to foster adherence to unsupervised training, including SMS reminders, effective time management strategies (e.g. diarizing sessions into a routine schedule), motivational cues and rewards [60‐62], and other behavior strategies [63‐65].

All reported adverse events were not related to the study intervention indicating that PRT is safe intervention for women with PCOS. This finding is consistent with the evidence base in other chronically diseased cohorts, including type 2 diabetes [66‐70].

In general, the completion of clinical outcomes assessments was satisfactory in the present study. However, the administration of weekly status checks via email and telephone to monitor adverse events in the control group proved problematic with only 58 % completed. This may be improved by arranging weekly visits with participants, if feasible.

The PRT intervention applied in the present study yielded a number of clinically important adaptations that may be associated with better disease management and treatment of the underlying pathology. No significant change in menstrual cyclicity was noted in the PRT or control group. However, studies of aerobic training [47, 52] and dietary and exercise intervention, including those involving aerobic plus PRT [51] have shown improved menstrual cyclicity using similar methodology (i.e. self-reported menstrual diary). There is reason to hypothesize that PRT can improve menstrual cyclicity in women with PCOS [24]. Therefore, future studies should continue to investigate this endpoint in women with oligo/amenorrhea, including the dosages of PRT required to induce adaptation. Such investigations require vigilant monitoring of menstrual cycles (i.e. date of last menstrual period in women with amenorrhea and documenting menstrual cycle length in women with oligomenorrhea and regular cycles) and reporting of confounding variables including physical activity and dietary habits.

PRT may counteract the etiology of PCOS through its effect on body composition [24]. Improvements in skeletal muscle size and quality secondary to PRT in type 2 diabetes have been accompanied by reductions in visceral fat [67, 71] and improvements in insulin sensitivity and glucoregulation [67, 71‐73]. Increased insulin sensitivity and glucoregulation, in turn, may downregulate androgen synthesis and hyperandrogenemia in women with PCOS, which could counteract the disease process (i.e. premature growth arrest of follicles) and menstrual irregularity [24]. The anthropometric changes experienced by the PRT group in the present study, including the reduction in waist circumference (p = 0.03) and increase in fat-free mass (p = 0.005) were accompanied by an improvement in HbA1c (p = 0.031) versus the control group, indicating parallel improvement of body composition and glucoregulation. However, the PRT group experienced no change in HOMA-2, several key endocrine markers (i.e. free androgen index [p = 0.18], testosterone [p = 0.91], SHBG [p = 0.246]) or other key haemotological markers associated with PCOS (i.e. CRP, fasting insulin) versus the control group (Table 2). These physiological data are difficult to interpret within a small-scale study. Future studies are required to investigate these adaptations, including the determination of dose-response effects for each outcome. These studies would also benefit from using more sensitive measures of insulin resistance, including the euglycaemic-hyperinsulaemic clamp [74], and gold-standard assessment of steroids involving liquid chromatography-tandem mass spectrometry [75] with the standardisation of assessments to a particular phase of the menstrual cycle (i.e. day 2-5 of menstrual cycle), if required.

Unexpectedly, within group analyses showed that the PRT group increased fasting glucose over time (p = 0.03). This finding may be reflective of an acute effect, i.e. in response to psychological stress or lack of sleep. Previous studies in PCOS, type 2 diabetes and/or obesity that prescribed aerobic, mixed training, and/or diet plus exercise have reported significant reductions in fasting insulin and fasting glucose [46, 47, 52, 76‐79] and therefore this outcome requires further exploration in PCOS.

The PRT group demonstrated a trend toward increased upper body strength (p = 0.06) and a significant rise in lower body strength (p = 0.03) compared to the control group. PRT is the modality of choice for eliciting strength gains [80, 81] and these adaptations are typically accompanied by improvements in performance-based tests and psychological attributes, including HRQoL [40, 82, 83]. Women with PCOS have been shown to have greater muscular strength than their healthy peers [84] and future studies are required to determine the clinical importance of strength adaptation in this cohort.

The PRT group improved three of five PCOSQ domains versus the control group: emotions (p = 0.003), weight (p = 0.04) and infertility problems (p = 0.03). In addition, the PRT group significantly improved five of eight HRQoL (SF-36) domain scores (physical functioning [p = 0.02], vitality [p = 0.02], social functioning [p = 0.002], role emotional [p = 0.009] and mental health [p = 0.009]), DASS-21 domains for depression (p = 0.01) and anxiety (p = 0.03), and exercise self-efficacy (p = 0.035) versus the control group. The psychological benefits of exercise or physical activity in women with PCOS have been noted previously and are clinically relevant [85, 86]. Future studies involving placebo-control groups are required to determine if these psychological adaptations can be attributed solely to the PRT, or are influenced by the social interaction with trainers and/or other participants.

In summary, a randomized clinical trial of PRT in PCOS would be feasible to conduct, and this mode of exercise may elicit a therapeutic effect on a range of pertinent outcomes in this cohort. A suitably powered clinical trial is required to confirm these findings and answer novel research questions in relation to prescribing PRT as a therapeutic intervention in PCOS. The success of a large-scale trial required to confirm these findings would be contingent on addressing the feasibility hurdles identified in this study with respect to recruitment, attrition, compliance, and collection of standardized clinical data.

The Human Research Ethics Committee at Western Sydney University (reference H10448) approved all procedures, and written informed consent was obtained from all participants.