In this quasi-experimental study, 24 women diagnosed by PCOS were recruited. The study was conducted at a university hospital which is a tertiary referral centre with services for gynaecological disorders affiliated to Kermanshah University of Medical Sciences, Kermanshah, Iran. The study started from March 2017 and ended in September 2017.

During the study period, 24 women diagnosed by PCOS who agreed to participate in the study and provided blood samples were consecutively included. They were divided into HIIT group (12 cases) and control group (12 cases) who did not receive any intervention. The control group was instructed to resume routine daily lifestyle and diet.

Inclusion criteria were PCOS patients diagnosed or with a history of symptoms of PCOS for more than six months within age range of 20 to 40 years and not being involved in any other exercise training (during the preceding two months before study initiation) or physiotherapy/rehabilitation courses and without other chronic conditions such as infectious, immune disorders, musculoskeletal conditions, cardiovascular/neurologic/psychiatric diseases and visual disturbances. The diagnosis of PCOS was made according to the Rotterdam criteria [17]. According to the criteria, three factors are assessed by clinical, imaging, and biochemistry (oligo- and/or anovulation, clinical and/or biochemical signs of excess androgen, polycystic ovaries). If at least two of these criteria are present, the diagnosis of PCOS is confirmed.

Exclusion criteria were Cushing syndrome and androgen-secreting tumours, using walking aid devices, endocrine disorders such as hyperprolactinemia and hyperthyroidism, use of oral contraceptive, anti-diabetic, anti-androgenic treatments and oocyte induction or any corticosteroid substance within the past 30 days, pregnancy, smoking and alcohol consumption.

First, the goals of the study and the stages of the research were described for the subjects. After obtaining a letter of informed consent from the subjects, they were included. The study proposal and details were verified by the Ethics Committee of Kermanshah University of Medical Sciences, Kermanshah, Iran with the ethics code IR.KUMS.REC.1397.573.

HIIT is a type of interval training (in comparison to continuous training) where subjects perform intermittent short bursts of high-intense anaerobic exercises with recovery periods between these short periods. During the recovery periods, the subjects perform less intense activity or they may rest [18]. In this study, HIIT was scheduled for 12-weeks (3 sessions per week). Of three weekly sessions, two sessions were planned with four stages of four-minute running with the goal of achieving 90 to 95% of maximum heart rate (reflecting high-intensity training). These four high-intense stages were separated by three stages of less-intense (moderate intensity) running with the goal of achieving a heart rate equal to 70% of maximum heart rate [Table/Fig-1]. One weekly session was scheduled with 10 periods of one-minute high-intense running separated by 10 one-minute periods of restring. The subjects performed the exercises in an indoor sports gym.

[Table/Fig-1]:

High intensity interval training with four stages of four-minute training with three moderate intensity stages between them.

The third session consisted of 10 stages of one-minute exercise with maximum intensity separated by a very low activity or one-minute rest stages between the high intensity stages [Table/Fig-2].

[Table/Fig-2]:

High intensity interval training with 10 stages of one-minute training with intervals of moderate exercise or rest between them.

The patients of HIIT group were instructed about the method of doing the exercises. In order to monitor and ensure that the HIIT program, each week the patients were randomly selected and contacted in presence to monitor the exercise training sessions.

First, before the beginning of the study, hs-CRP, fasting insulin and fasting glucose levels were measured. These measurements were repeated 48-hours after completion of the study. About 3 mL of venous blood samples were taken from the anterior cubital vein. Sampling was performed at a specific time of day (8 to 10 AM), so that the level of insulin and CRP is not affected by its overnight fluctuations. Blood samples were centrifuged for 15 minutes at a rate of 3000 rpm and stored at -80°C. Measurement of fasting insulin level was done by sandwich ELISA using the isotope kit. Immunoturbidimetry was used to measure hs-CRP.

Homeostatic Model of Assessment of Insulin Resistance (HOMA-IR) was used to determine insulin resistance [19].

The participants were weighted using Seca Digital Weigh with 0.1-kg precision. The subject’s height was measured by using measurement tape fixed on the wall with minimum 0.1 centimetres. The BMI was calculated as body weight in kg divided by height in meters squared.

Descriptive indices (mean, standard deviation, frequency, and percentage) were used to describe the variables. Paired t-test was used to compare HOMA-IR and hs-CRP levels before and after HIIT. Student’s t-test was used to compare continuous variables between the two study groups. Statistical analyses were performed by SPSS software (version. 22.0) and significance level was considered as 5%.

A total of 24 female patients were studied. There was no statistically significant difference regarding baseline variables between the two groups [Table/Fig-3].

There was a significant decrease in hs-CRP (25.4% decrease from baseline) and HOMA-IR (38.1% decrease from baseline) in the experimental group after HITT. However, no significant change was observed in control group [Table/Fig-4].

Chronic mild inflammation and metabolic abnormalities such as insulin resistance are associated with PCOS. Efforts have been made to investigate different interventions to improve insulin sensitivity and reduce inflammation. One such intervention is exercise training in the form of aerobic exercise or resistance training. The aim of this study was to determine the effect of 12-weeks of HIIT on the levels of insulin resistance and hs-CRP in women with PCOS. The results of the study showed that after 12-weeks of HIIT, both insulin sensitivity (a decrease in HOMA-IR) and hs-CRP levels improved significantly in this group. However, no meaningful change was seen in control group that did not receive any intervention. The results of this study are consistent with the results of some previous studies. In a previous study, including two methods of exercise training (strength training and HIIT) on eight PCOS patients, mean hs-CRP decreased from a baseline value of 3.2 mg/L to 2.4 mg/L which was not statistically significant [16]. In the mentioned study [16], other inflammatory markers (adiponectin and leptin) similar to hs-CRP did not change significantly. However, in agreement with the present findings, HOMA-IR improved significantly in HIIT group and deceased from a baseline mean value of 4.9 to 4.1. As stated previously, inflammation has been suggested as a mechanism for insulin resistance in PCOS patients. This was the reason that it was decided to measure HOMA-IR index as well as hs-CRP to find out whether any changes can occur in both of them. However, considering the results of the mentioned study [16] that HOMA-IR decreased and hs-CRP did not change, it may be concluded that other factors contribute to insulin resistance and inflammation is not the sole mechanism underlying inflammation in PCOS.

In another study by Thompson RL et al., comparing three interventions (diet, diet and exercise, and combined aerobic-resistance exercise) in PCOS patients, mean HOMA value at baseline was 2.04 which decreased to 1.41 after 20 weeks of combined aerobic-resistance training which was significant [15]. This finding is compatible with the current findings, although the methods of exercise training programs are different. In this study, only the effect of resistance training was studied. The women did not perform aerobic exercise. As mentioned above different exercise methods and settings is a major factor when comparing the findings between different studies. Hutchison et al., [10] investigated 12-weeks of intensified exercise intervention (three hours weekly) on two groups of women with (13 subjects) and without (eight subjects) PCOS. All subjects had BMI of more than 27 kg/m². In PCOS group, HOMA had a median of 5 [interquartile range=3.7 to 8.2] at baseline. Although this decreased to 3.4 [2.3 to 9.2], the change was not statistically significant (p=0.43). This finding is not compatible with the present results. The difference could be attributed to several factors. The subjects in the present study mostly had normal BMI with a mean value of 21 kg/m² in HIIT group. However, all patients in the mentioned study [10] had BMI of >27 with an average of 35 kg/m² which significantly decreased after 12-weeks of exercise. Despite this decrease in BMI value, visceral fat did not change. This highlights the role that visceral fat plays regarding insulin resistance. However, the authors [10] did not show a causational relationship between visceral fat and insulin resistance. As study designs and frequency and intensity of exercise programs differ among studies, there is still a need for further well-controlled studies to reach definite conclusions. Another issue that should be considered in PCOS patients is that insulin resistance may not be necessarily present in all PCOS patients irrespective of their BMI. Besides, those with insulin resistance may have varying severities of insulin resistance. Some studies have determined combined effect of diet and energy restriction in addition to physical exercise in PCOS women [20]. As here the present authors did not control the diet of the subjects and only physical exercise was selected as the intervention, head-to-head comparisons cannot be made with studies that controlled both diet and physical exercise. In addition, not all PCOS women have obesity and BMI values greater than 25 kg/m². Since many patients with PCOS may have BMI values in the range of obesity, many former studies have recruited PCOS patients with obesity [10,16].

An important mechanism proposed for the role of exercise in insulin resistance is the glucose uptake by skeletal muscle which occurs via activation of signalling pathways [21]. Exercise can stimulate molecular signalling pathways and by facilitating GLUT4 expression, ultimately leads to glucose transport into the cell [22]. This mechanism is extensively studied in diabetic patients. The signalling pathways are dependent on insulin action and the skeletal muscle is the main site of this action. Besides, insulin resistance is well established to have correlation with visceral fat [23]. The change in the weight of the patients was not evaluated to determine whether abdominal fat had correlation with the observed findings. Insulin resistance is a major biochemical concern in obese patients as well as in PCOS patients. Insulin resistance can have consequences regarding cardio-metabolic outcomes. Therefore, it should be managed properly in PCOS patients to prevent development of future metabolic abnormalities such as T2DM. As mentioned earlier, there is controversy regarding initiating metformin routinely in PCOS patients. Therefore, non-pharmacologic therapies such as HIIT not only can have beneficial effect on insulin resistance but can have other benefits for overall health.

It is recommended that in the future studies, clinical trials with larger sample size with randomisation and longer follow-up be performed to overcome the limitations encountered in this study. In addition, controlling the diet of the patients, will provide more robust information about the role of exercise training. In addition having different exercise training programs will enable us to compare the feasibility and efficacy of different methods of exercise to find out which training has the best outcome.

There were certain limitations in this study. First, except for hs-CRP, other inflammatory markers were not measured. Also, body composition and weight changes were not investigated. In addition, more patients were not accessible for inclusion in the study and randomisation was not implemented here. However, as BMI was comparable between the two groups at baseline, it could be concluded that weight and body position may not have significant effect on the findings. Also, the diet of the patients was not controlled in either group and calorie counting was not performed.

HIIT for 12-weeks had significant effect on insulin sensitivity and hs-CRP in PCOS patients. These findings confirm the beneficial role of regular resistance exercises in improving insulin sensitivity. It is suggested that PCOS women perform resistance exercises.