Feasibility of Targeted Case-Finding of Polyendocrine Metabolic Ovarian Syndrome in the Workplace: A Pilot Cohort Study

Highlights

Public health relevance—How does this work relate to a public health issue?

• Polyendocrine metabolic ovarian syndrome (PMOS) affects one in eight women of reproductive age and is underdiagnosed and treated late.
• PMOS causes increased cardiovascular risk, sleep disorders, mental health problems, eating disorders, reduced fertility, and promotes uterine and ovarian cancer.

Public health significance—Why is this work of significance to public health?

• Health surveillance of working women is a useful opportunity to detect those who have symptoms compatible with PMOS and refer them for tests to confirm the diagnosis.
• The dietary measures and physical activity that are recommended for women with PMOS can be disseminated among all working women to the benefit of all concerned.

Public health implications—What are the key implications or messages for practitioners, policymakers and/or researchers in public health?

• Occupational physicians should actively look for symptoms of PMOS in periodic workplace medical examinations.
• Collaboration between occupational physicians and specialists in the treatment of PMOS could substantially improve the quality of life and working lives of patients.

Abstract

Polyendocrine metabolic ovarian syndrome (PMOS) is the most common endocrine disorder in working women. Workplace screening could contribute to the early diagnosis and treatment of this chronic condition. Fertile women who participated in a 2022 health food promotion campaign and had suspected eating disorders, overweight/obesity, metabolic abnormalities, sleep problems, or mental health concerns were interviewed about PMOS symptoms during their in-office medical examination. Twenty-eight of the 1170 women examined had symptoms of suspected PMOS. By 2023, 21 of these diagnoses had been confirmed by specialists. The prevalence of newly diagnosed PMOS among the women of childbearing age was 2.7% (CI95% 1.7; 4.2). The confirmation rate of the clinical suspicion of PMOS was 75% (CI95% 55.1; 89.3). Female workers with newly identified PMOS had a significantly higher frequency of eating disorders than their pre-menopausal colleagues and higher body mass index values, higher glycemia, and higher cholesterol values. PMOS patients also had higher depression symptom scores than other workers of childbearing age. In conclusion, with a short interview during mandatory medical examinations, the occupational physician can make a significant contribution to the diagnosis of PMOS, thereby hopefully improving the quality of life of women and reducing damage to their health.

1. Introduction

Polycystic ovarian syndrome (PCOS), now known as polyendocrine metabolic ovarian syndrome (PMOS) [1], is the most common endocrine-metabolic disorder affecting females across their lifespan. A meta-analysis calculated a global prevalence rate of 9.2% (95% confidence interval, 95%CI: 6.8–12.5%) with significant geographical differences influenced by lifestyle and environmental factors [2]. This means that roughly one in eight women workers of reproductive age, and over 170 million women worldwide, are affected by PMOS [3]. In addition to gynecological symptoms associated with oligo-anovulation (irregular cycles, flat basal temperature, lack of painful ovulatory symptoms and ovulatory cervical mucus, sexual dysfunction [4] and possible infertility [5,6,7]) and dermatological symptoms associated with hyperandrogenism (hirsutism, acne and oily skin, acanthosis, alopecia and male hair pattern) [8,9,10], it also impacts on metabolic problems (hyperinsulinemia [11], diabetes [12], overweight or obesity [13], hypertension [14], dyslipidemia [15], metabolic syndrome [16], non-alcoholic fatty liver disease [17,18], cardiovascular disease [19,20]), sleep disturbances (sleep apnea, insomnia) [21,22], mental health [23] and eating disorders (EDs) [24]. PMOS leads to a high atherosclerotic risk (adjusted hazard ratio, aHR = 4.40; 95%CI = 4.23–4.58), regardless of the presence of other metabolic diseases, as demonstrated by the extensive longitudinal study conducted by Alur-Gupta et al. in the USA [25]. The syndrome is also associated with an increased risk of developing endometrial and ovarian cancers [26]. The complexity of the clinical picture has recently led to classifying the condition as an endocrine-metabolic disease rather than a reproductive one [27,28]. According to international guidelines, diagnosis requires the presence in adults of at least two of the following criteria: (1) oligoanovulation, (2) hyperandrogenism, and (3) polycystic ovaries on ultrasound or elevated anti-Müllerian hormone (AMH) [29,30]. Early diagnosis is particularly useful because treatment significantly improves the quality of life of patients [31].

Unfortunately, early diagnosis is not always achieved, even in highly developed countries. Women often overlook the symptoms of ovulatory irregularity, addressing instead skin problems with cosmetic measures and obesity with dietary measures so that detection and a correct diagnosis may be eluded. Diagnostic delays could affect between one-third [32] and more than two-thirds of cases [33,34,35,36]. Moreover, patient management is often unsatisfactory. In the UK, a recent parliamentary report highlighted the fragmented care that often affects those with PMOS [37]. Studies indicate that patients still experience substantial gaps in risk awareness, monitoring, and counseling [38]. Generally, women are evaluated by several specialists from endocrinology, dermatology, gynecology, and fertility services, without any coordination, and PMOS diagnosis is frequently disregarded in primary care. There is clearly a need to integrate the various investigations and merge them into a well-defined project. Health surveillance in the workplace can offer a solution to this problem.

In Italy, occupational health services offer most workers periodic health checks. These checks are mandatory under European regulations to assess whether workers might be exposed to occupational risks and are therefore intended for preventive purposes. However, they are increasingly associated with health promotion projects, following the philosophy known in the US as Total Worker Health (TWH©) [39] and in Italy as integrated promotion and prevention (PIP) programs [40]. These interventions are free for workers and generally achieve very high participation rates [41]. In this way, they become a kind of survey of the health status of workers. The data collected by health surveillance services enable occupational physicians to integrate the different aspects of health and give workers personalized advice, including lifestyle and activity modifications, as well as referrals for specialized treatments available at National Health Service units.

Considering the high prevalence of PMOS among working-age women and its high health and economic cost [42,43,44], we decided to conduct targeted case-finding in the workplace. Since the condition affects very sensitive aspects of sexual and reproductive life, we deemed it appropriate to investigate through verbal interviews rather than questionnaires. Based on data from a survey on eating habits and eating disorders (EDs), we selected for these interviews those individuals most likely to have the syndrome, since it is known that EDs and PMOS can be associated.

The literature indicated that women with PMOS were 3–6-fold more likely to have an ED and had higher odds ratios (ORs) of an elevated ED score compared with controls [45]. Disordered eating in PMOS is often associated with emotional eating and obesity [46] and with metabolic syndrome [47]. PMOS is also associated with sleep problems, such as insomnia [48] and obstructive sleep apnea syndrome (OSA) [49]. Of clinical significance is the association with anxiety and depression [50], and with migraine and endometriosis [51]. This constellation of comorbidities is an expression of the polyendocrine nature of the syndrome. In the workplace, where eating habits, metabolic status, and mental health can be monitored, suspected cases of PMOS can be revealed by identifying the associated problems.

Starting from this knowledge, we designed our pilot study as a development of the EDs campaign: we selected women with suspected EDs, obesity, and metabolic syndrome components and investigated during their routine medical examination in the workplace the presence of symptoms compatible with a diagnosis of PMOS. The primary aim of the campaign was to identify women who might have PMOS and invite them to confirm the diagnosis through the National Health Service facilities. A secondary goal was to monitor the anthropometric measurements and physical activity levels of PMOS cases in the workplace. Long-term treatment of PMOS requires improved diet and exercise regimens. The inclusion of PMOS case-finding within a food health promotion campaign seemed appropriate to disseminate appropriate dietary measures and physical activity programs among female workers, regardless of the presence of PMOS.

2. Materials and Methods

2.1. Population

Workers who were monitored by the Catholic University of the Sacred Heart of Rome, Italy, in 2022 were invited to participate in a health promotion program that included screening for eating disorders (EDs). They belonged to 42 companies, primarily small (fewer than 50 employees) or micro-businesses (fewer than 10 employees) that represent 99% of active companies in Italy. Workers performed a wide variety of tasks with varying degrees of responsibility. Occupational hazards included biological agents, manual handling of loads, night work, ionizing and non-ionizing radiation, work with video terminals, and numerous others. In total, 91.7% of the 2085 workers agreed to participate. Of these, 1170 were female; their ages ranged from 22 to 70 years (mean 44.6 ± 11.7 years), and 767 (65.6%, mean age 37.3 ± 7.9 years) were of childbearing age, that is, they were still menstruating, even if some were over the age of 44, which the Centers for Disease Control and Prevention indicates as reproductive age. The results of the cross-sectional population-based project have been published [52,53,54]. The survey allowed us to identify the female workers who were most likely to be suspected of having PMOS and invite them for an in-depth interview. The interview identified those women of childbearing age suspected of having PMOS, who were then followed for one year, until the next periodic medical examination. The cohort study followed the STROBE guidelines [55] (Table S1).

The research was authorized by the Ethics Committee of the Catholic University of the Sacred Heart, Polyclinic A. Gemelli Foundation, Rome, on 3 March 2022 (ID 4671).

2.2. Questionnaire

At the baseline, the entire cohort completed the Italian version [56] of the Eating Disorder Examination Questionnaire, short form (EDE-QS) [57,58]. This instrument is composed of 12 questions with answers classified according to a 4-point Likert scale ranging from 0 to 3. It demonstrated good stability and gender invariance [59]. According to DSM 5 criteria, workers who have reported an EDE-QS score greater than 15 [60] can be considered suspected ED cases. Additionally, the questionnaire can predict the kind of disorder and differentiate between suspected anorexia nervosa, bulimia nervosa, and binge eating disorder by using body mass index (BMI). The questionnaire’s Cronbach’s alpha in this study was 0.841.

Sleep quality was assessed using the Italian version [61] of the Pittsburgh Sleep Questionnaire Index (PSQI) [62]. The questionnaire consists of 18 items leading to 7 components, with a score that can vary from zero to 21 points. A score above 5 points indicates poor sleep quality [63]. In this study, Cronbach’s alpha for the PSQI was 0.828. We investigated the risk of obstructive sleep apnea (OSA) by following the guidelines of the Italian Interdisciplinary Technical Committee for Sleepiness and Safety in OSA patients [64], which recommended, for large surveys, the adoption of two binary questions from the STOP-Bang questionnaire [65,66] to formulate a suspicion of obstructive apnea.

Anxiety and depression were assessed using the Italian version [67] of the Goldberg Anxiety and Depression Scale (GADS) [68], consisting of 18 binary questions. Both subscales range from 0 to 9. A score above 5 points on the anxiety scale and above 2 points on the depression scale indicates a greater than 50% chance of having a clinically important disturbance. Both subscales showed good reliability, 0.826 for anxiety and 0.811 for depression.

Anthropometric measurements (height and weight) were taken during medical examinations in accordance with the International Society for the Advancement of Kinanthropometry (ISAK) criteria [69]. The body mass index (BMI) was calculated as the ratio between weight and height squared. Participants’ blood pressure was monitored using three consecutive readings, and a final average was calculated after they had been seated for at least five minutes. According to the 2023 European Hypertension Guideline Update [70] and the American College of Cardiology [71], systolic pressure over 140 mmHg, diastolic pressure over 90 mmHg, or continuous antihypertensive treatment were considered indicators of hypertension. Levels of blood glucose, triglycerides, total cholesterol, and HDL cholesterol were measured. Cut-off levels of metabolic parameters were determined, taking into account the International Diabetes Federation (IDF) [72], the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (NCEP/ATPIII) [73], the American Association of Clinical Endocrinologists (AACE) [74], and the Joint Societies Guidelines on Management of Cholesterol [75]. Indices of hypercholesterolemia were defined as total cholesterol above 200 mg/dL (5.2 mmol/L) or HDL cholesterol below 40 mg/dL (1.03 mmol/L) in men and below 50 mg/dL in women, or treatment for hyperlipidemia. Hypertriglyceridemia was defined as a serum triglyceride level exceeding 150 mg/dL (1.7 mmol/L). High fasting glucose was defined as a plasma glucose level above 100 mg/dL (5.6 mmol/L) or the use of hypoglycemic medication.

2.3. Medical Examination

The in-depth interview to evaluate the possibility of ovarian dysfunction was conducted with all women of childbearing age with suspected EDs, those with EDE-QS scores close to the cut-off for EDs, and those reporting overweight or obesity, metabolic imbalances, sleep or mental health problems, and no natural or iatrogenic menopause. The structured interview lasted between 30 and 45 min and took place during the medical examinations carried out at the workplace. The questions were taken from the Pedersen [76] and Kalra [77] questionnaires, which have been used as self-compiled screening tools for PMOS diagnosis [78]. Pedersen’s questionnaire collects 4 symptoms: variable or long (≥35 days) menstrual cycles; coarse hair at 3 or more sites; history of obesity; lactation unrelated to pregnancy. The Kalra questionnaire (9 items) adds questions about subfertility and early pregnancy loss, glycemic and cardiovascular problems, and dermatological alterations. The questions were posed in a conversational manner to explain the reasons for the study and to immediately provide any necessary advice. Questions were classified into three sections: menstrual/maternal, metabolic, and dermatological symptoms (

Table 1. Topics covered in the structured interview.

Menstrual/Maternal	Metabolic	Misfit Masculinity (Dermatological)
Do you have variable or very long menstrual cycles?	Have you suffered from or are you suffering from obesity?	Do you have unwanted hair on various parts of your body?
Do you have irregular, sometimes minimal, menstrual flow?	Do you have hyperinsulinism?	Do you suffer from acne?
Have you had or are you having difficulty conceiving, after 12 months of unprotected intercourse?	Do you have high blood sugar, an abnormal glycated hemoglobin test (≥5.7%), or have you been diagnosed with prediabetes?	Do you have thicker, darker-than-normal skin in the creases of your armpits, groin, or other parts of your body? (Do you suffer from acanthosis nigricans?)
Have you had an early pregnancy loss?	Do you have high blood pressure or are you treating it?	Do you have thinning or hair loss, with a receding hairline or thinning crown?
	Do you have high cholesterol or triglycerides, or are you treating them?	Have you had or do you have milky nipple discharge unrelated to pregnancy?

).

The Pedersen and Kalra questionnaires were used as a framework for the interview between the occupational physician and the worker. The conversation developed differently on a case-by-case basis, considering the elements of each woman’s individual history, such as reproductive history, use of drugs and hormone treatments, and surgical procedures. No algorithm was applied, as would have been necessary for a self-completion questionnaire. At the end of the interview and medical examination, the doctor was able to formulate an eventual clinical suspicion of PMOS. The criterion for suspicion was the presence of clinical signs of both ovulatory dysfunction and hyperandrogenism. Female workers who exhibited symptoms consistent with a diagnosis of PMOS were advised to contact their general practitioner for further testing through the National Health Service (NHS). During the subsequent medical examination at the workplace, they were questioned about the results of the diagnostic and therapeutic process. All workers were examined for the first time in 2022 and a second time in 2023.

2.4. Statistics

We studied the distribution of the variables of interest using the Kolmogorov–Smirnov and Shapiro–Wilk tests to verify whether they followed the normal distribution. According to Lumley [79], the sample size gave us confidence that parametric techniques could be applied even when the variables were ordinal in nature; however, we resorted to robust methods when this assumption was not met. The Clopper–Pearson exact binomial test [80,81,82,83] was used to determine the degree of uncertainty (confidence intervals, 95%CI) in prevalence rates. Comparisons between the frequencies observed in the subgroups were made by applying the chi-square test. Comparisons between means were performed with the Student’s t test and the Mann–Whitney U test. The size of the difference between means was evaluated by Cohen’s d. Statistical analyses were performed with the IBM SPSS statistical package, Armonk, NY, USA, version 31.0.

3. Results

The picture resulting from medical examinations and analyses allowed us to verify the presence of health problems in the population (

Table 2. Prevalence of pathologies observed in the sample and in the subgroups of fertile and post-menopausal women.

	Whole Group, N = 1170 n (%)	Fertile Women, N = 767 n (%)	Post-Menopausal Women, N = 403 n (%)	p 1
Suspected EDs	62 (5.3)	28 (3.7)	34 (8.4)	<0.001
Central/Waist obesity	196 (16.8)	102 (13.3)	94 (23.3)	<0.001
Hyperglycemia	139 (11.1)	51 (6.6)	88 (21.8)	<0.001
Hypertension	228 (19.5)	87 (11.3)	141 (35.0)	<0.001
Hypercholesterolemia	320 (27.4)	119 (15.5)	201 (43.9)	<0.001
Hypertriglyceridemia	72 (6.2)	34 (4.4)	38 (9.4)	<0.001
Metabolic syndrome	109 (9.3)	37 (4.8)	72 (17.9)	<0.001
Low sleep quality	603 (51.8)	365 (47.7)	238 (59.9)	<0.001
Suspected OSA	111 (9.5)	55 (7.2)	56 (13.9)	<0.001
Anxiety	259 (22.3)	139 (18.1)	120 (30.2)	<0.001
Depression	395 (33.9)	223 (29.1)	172 (43.2)	<0.001

¹ Chi-square test. N= number of cases in the group; n = number of cases in each category.

). As expected, post-menopausal female workers had a significantly higher prevalence of metabolic syndrome components, sleep disorders, and mental health problems than women of childbearing age.

Sixty-two female workers (5.3%, CI95% 4.1; 6.7) had a score above the EDE-QS cut-off, indicating suspected EDs. None of these cases were associated with a body mass index (BMI) lower than 17.5, which is consistent with a diagnosis of anorexia nervosa. Almost all the women with a high EDE-QS score had BMIs above 18.5, suggesting a diagnosis of bulimia nervosa (BN) or binge eating disorder (BED). One woman with a high EDE-QS score and normal BMI was suspected of reporting other specified feeding or eating disorders (OSFED).

Cases of suspected EDs were also more frequent among older women than among younger working women. ED comorbidities were more common among the older workers than among the women of childbearing age (

Table 3. Comorbidity of EDs.

	Whole Group N (%)	Fertile Women N (%)	Post-Menopausal Women N (%)	p 1
ED + obesity	24 (2.1)	7 (0.9)	17 (4.2)	<0.001
ED + hyperglycemia	18 (1.5)	7 (0.9)	11 (2.7)	<0.001
ED + MetS	12 (1.0)	3 (0.4)	9 (2.2)	<0.001
ED + poor sleep	47 (4.0)	22 (2.9)	25 (6.2)	<0.001
ED + OSA	18 (1.5)	11 (1.4)	7 (1.7)	<0.001
ED + depression	45 (3.8)	21 (2.7)	24 (6.0)	<0.001

¹ Chi-square test. N = number of cases in each category.

).

During medical examinations conducted at the workplace after interviews, 28 women were suspected of having PMOS, as they reported symptoms of hyperandrogenism and ovulatory irregularities. Of these workers, 14 had suspected EDs and associated metabolic disorders; the others had endocrinological problems, overweight, alterations in the menstrual cycle, and dermatological problems. They were sent by their general practitioners for further specialist tests, including ovarian ultrasonography, anti-Müllerian hormone (AMH) dosage, hormonal testing, endocrinological and gynecological consultations, to confirm or exclude the diagnosis.

At the subsequent periodic examination, 21 workers reported having been diagnosed by a gynecologist and/or endocrinologist with PMOS (proportion of newly identified cases among women of childbearing age: 2.7%, CI95% 1.7; 4.2). The suspected diagnosis was confirmed by specialists in 75% of cases (CI95% 55.1; 89.3). The women were under dietary control and had increased physical activity. They also followed the treatments suggested by their attending physicians to control metabolic and mental health comorbidities. Of the seven cases for which the suspicion of PMOS was not confirmed at the 2023 visit, one declined further diagnostic evaluation because they had gone into menopause, two had ceased employment and had not completed the diagnostic assessment, and four were found not to have PMOS by their physicians.

Female workers with a confirmed diagnosis of PMOS had significantly higher EDE-QS scores than their pre-menopausal colleagues (14.6 ± 8.2 vs. 4.6 ± 4.7, Student’s t p < 0.001; Mann–Whitney U p < 0.001). The effect size was large (Cohen’s d = −2.09; 95%CI −2.54; −1.65). The newly confirmed cases had higher mean BMI values (26.9 ± 5.2 vs. 23.3 ± 4.3; Student’s t, p < 0.001; Cohen’s d = −0.84; 95%CI −1.32; −0.35) than other fertile women. They also had higher glycemia (120.5 ± 49.3 vs. 81.7 ± 25.2, Student’s t p < 0.001; Cohen’s d = −1.46; 95%CI −2.10; −0.81) and higher cholesterol values (232.7 ± 24.5 vs. 181.6 ± 37.7, p < 0.001; Cohen’s d = −1.36; 95%CI −2.04; −0.686) than their colleagues. Confirmed PMOS patients also had lower sleep quality scores (PSQI score 7.6 ± 5.0 vs. 5.6 ± 3.1, Student’s t p = 0.005; Cohen’s d = −0.62; 95%CI −1.06; −0.19; Mann–Whitney U p = 0.75) and higher anxiety scores (4.1 ± 3.3 vs. 2.8 ± 2.6, Student’s t p = 0.019; Cohen’s d = −0.518; 95%CI −0.952; −0.083; Mann–Whitney U p = 0.073) but the effect size of the difference was not large and the nonparametric tests approximated significance without reaching it. Newly diagnosed PMOS cases had higher depression symptom scores (3.3 ± 2.6 vs. 1.7 ± 2.1, Student’s t p < 0.001; Cohen’s d = −0.78; 95%CI −1.22; 0.348; Mann–Whitney U p = 0.004) than other workers of childbearing age.

Twelve of the women with confirmed PMOS had an EDE-QS score indicative of eating disorders. Thirteen workers with confirmed PMOS were depressed, six had a score indicating anxiety, thirteen had poor sleep quality, and three had sleep apnea. Eleven workers suffered from PMOS, EDs, and depression, and six of them combined eating and psychiatric problems with sleep problems. Ten of the women with PMOS were obese, six of them also had eating disorders, and five also had depression. PMOS was often associated with metabolic problems; five of the confirmed cases had increased blood pressure, ten had low HDL cholesterol or high total cholesterol, four had high triglycerides, sixteen had high blood glucose, and eight had metabolic syndrome.

4. Discussion

Developed as an addition to a health food promotion program, this study demonstrated the feasibility of targeted case-finding of PMOS in the workplace. Medical interviews conducted with women who had eating disorders, obesity, or metabolic disorders detected suspected cases of PMOS, which were confirmed by subsequent instrumental and laboratory tests in 75% of cases. The high positive confirmation rate of our clinical interviews appears to support extending the use of such structured interviews during workplace medical examinations to help detect undiagnosed cases.

The medical examinations and interviews were conducted by a single physician, the author of the article, a specialist in occupational medicine with no specific knowledge of this condition. Therefore, the confirmation of diagnosis and the treatment were entrusted to specialists from the National Health Service, and the occupational physician merely initiated the procedure and recorded the outcome a year later. This very simple procedure can be applied by any doctor in other companies.

The diagnosis of PMOS has long been hampered by differences in the definition of the condition. However, since 2003, the Rotterdam ESHRE (European Society of Human Reproduction and Embryology)/ASRM (American Society of Reproductive Medicine) Rotterdam consensus has established three criteria to simplify the diagnosis of the syndrome: ovarian dysfunction; hyperandrogenism; and the presence of ovarian cysts. PMOS can be diagnosed if the presence of at least two of the three parameters is confirmed. The third criterion, the presence of ovarian cysts, is the most difficult to meet. Observation of an increased number of follicles in the ovary is the gold standard in the ultrasonographic diagnosis of PMOS in adult women [84]. However, although arrested follicular development is common, pathological ovarian cysts are not always increased [85]. To overcome this difficulty, laboratory tests such as anti-Müllerian hormone (AMH) are usually carried out since the latter is a measure of ovarian reserve. An elevated level of AMH (>4 ng/mL), or a combination of circulating markers, could confirm clinical suspicion or add significance to a diagnosis of PMOS in cases of ambiguity [86]. Since it is not easy to diagnose PMOS, the support of artificial intelligence is considered to be useful [87,88,89,90]. While we acknowledge that a definitive diagnosis must be reserved for specialists in this disease, we are convinced that intervention on the part of the occupational physician is useful for showing workers their willingness to deal with health problems not directly caused by work, but which can interfere with work ability and the quality of life.

The interviews conducted in a setting rarely used for this type of testing allowed us to identify 21 cases of PMOS in female workers who were unaware of being affected by this insidious endocrine-dysmetabolic disease. After diagnosis, all the women followed personalized diet plans [91,92,93] and physical activity programs [94,95] recommended for this chronic condition. The treatment of PMOS cases generally results in significant improvements in the quality of life, body structure, and mental balance [96]. Improved health has a positive impact on productive capacity, which is significantly compromised in untreated PMOS. Women with PMOS have an approximately 25% poorer work ability and a two-fold higher disability retirement rate at midlife than their colleagues [97]. In the United States, 72% of women with PMOS acknowledge that the syndrome has impacted the quality of their work and more than half have had to miss work due to PMOS [98]. Moreover, PMOS is a significant predictor of cardiovascular risk in women of reproductive age [99], is associated with mental health disorders [100,101], and is significantly related to the risk of miscarriage [102]. Hyperandrogenism, which, alongside insulin resistance, is one of the main clinical features of the syndrome and of most cardiometabolic problems, tends to persist during the late-reproductive years and after menopause in women with PMOS [103]. In the United States, it was estimated that mental health problems associated with PMOS (anxiety, depression and EDs) led to costs exceeding $4 billion in 2021 and that the population expenditure for all pathologies associated with PMOS exceeds $15 billion per year [104]. Furthermore, PMOS is associated with a significantly increased risk of uterine and ovarian cancer [105,106,107]. Clinical experience indicates that weight loss and exercise, often difficult to maintain, can frequently help a woman to return to normal ovulatory cycles. Animal models also indicate that the removal of dietary determining factors induces self-healing [108]. However, only future epidemiological studies will be able to say whether PMOS treatment also reduces the risk of cancer. We are, nevertheless, certain that proper management of the disease offers significant economic benefits to workers, companies and society, and this justifies the implementation of workplace case-finding programs.

Occupational medicine activities are traditionally divided into preventive and promotional activities. The former are required by law and aim exclusively at preventing harm that could result from exposure to occupational hazards. The latter aim to improve the health of the workforce and benefit individuals, companies, and society. The doctor has an obligation to inform workers about the purposes of medical activities and obtain consent for their participation. In this study, there were no occupational risks that justified preventive action. The women who were the subject of our investigation were not occupationally exposed to endocrine disruptors [109] such as bisphenol A [110,111], phthalates [112,113], copper [114], cadmium [115] or other heavy metals [116], polychlorinated biphenyls (PCBs), organochlorine pesticides, polycyclic aromatic hydrocarbons (PAHs) [117] or other industrial agents [118] suspected of being associated with dysregulated ovarian function. The investigatory protocol set up for the prevention of occupational risks in all the companies where the study participants were employed did not include any examination concerning ovarian function. The health surveillance service decided to carry out a project to promote healthy eating. When this activity was proposed to companies and worker representatives, it obtained a very high participation rate among the workers. This participation in the promotion activity warranted extending the medical interview to include gynecological and endocrinological problems that were not part of their work-related symptoms and gave us the opportunity to use the medical resources available in the workplace for analyzing a segment of the population—young women—who often seek medical care only when acute problems arise. The workforce of childbearing age enjoys better health than the average working population. In fact, in our experience, chronic diseases are more frequent among older female workers. This well-known fact rightly suggests that disability management measures should focus mainly on older workers. However, this should not rule out efforts to identify chronic diseases in young people. Moreover, working women are more likely to delay their first pregnancy [119] and fail to seek medical treatment for fertility problems that are often the first symptom leading to a diagnosis of PMOS. Systematic screening for PMOS symptoms in the workplace can help to avoid overlooking these problems.

As is well known, medical interventions conducted in the workplace at the expense of the employer require legal, scientific, and economic validation. The law permits the development of health promotion programs in which workers participate voluntarily. Scientific evidence indicates that women with PMOS are more likely to develop EDs, have high average EDE-QS scores, and often experience overweight or obesity, sleep problems, poor mental well-being, and metabolic disorders. The significant impact of PMOS on work ability and productivity justifies the time spent on in-depth investigations during medical examinations conducted at the workplace.

The nutritional health promotion program with ED screening appeared to be particularly useful for identifying women with suspected PMOS. EDs are very common in adolescence or early adulthood [120], but tend to persist or recur [121], particularly in the peri-menopausal period [122]. Working women of childbearing age are therefore at high risk for EDs. EDs and PMOS are strongly associated [123,124]. Furthermore, it is worth remembering that health promotion programs are more likely to be successful if they propose positive goals such as improving one’s body image, shape and appearance, rather than negative ones such as diagnosing a chronic disease or checking for cancer [125,126]. For this reason, we proposed this PMOS targeted case-finding program as an addition to a nutritional program promoting positive health measures. Focusing on workers most likely affected by PMOS reduced the number of interviews and the time spent that interferes with production needs and obtained a high degree of specialist confirmation. The fact that confirmed cases had worse cardiometabolic and mental health indicators than their colleagues of childbearing age was widely expected, because the interviews had been focused precisely on workers with eating, metabolic, or emotional problems. Confirmed PMOS cases were likely those with greater metabolic and mental problems, and therefore those who require greater medical attention.

Conceptually, screening marks the transition from promoting healthy eating habits (the positive goal of the entire campaign) to early detection of clinical cases, which is really a secondary prevention activity. Occupational physicians can identify workers with complex chronic diseases, determine whether their work is compatible with their disability level, and ultimately monitor the progress of treatment. Since in this study we selected the workers for interviews based on eating and metabolic disorders, we probably selected the most clinically challenging cases. Interestingly, many of the workers had been treated for a metabolic problem, but none of them knew they had PMOS. We believe that a correct classification of the pathology helps to improve its treatment by coordinating the efforts of different specialists. The complexity of the observed cases, often associated with significant metabolic and neuropsychiatric problems, demonstrates that long-lasting disability management of the disease requires the participatory commitment of workers and careful occupational support, as occurs in other chronic pathologies [127,128].

An additional advantage of conducting clinical searching for suspected PMOS cases during the medical surveillance of workers is the chance to perform anthropometric measurements that are significantly correlated with insulin resistance and disease evolution [129]. Insulin resistance contributes to metabolic disorders like obesity, hyperglycemia, and dyslipidemia by dysregulating the metabolism of fats and carbohydrates [130]. Collaboration between the occupational physician and specialists can improve the clinical follow-up of patients and their job placement.

The complex array of endocrine and psychiatric disorders that can arise from PMOS demonstrates the value of early diagnosis and the potential benefits of workplace interventions. Unfortunately, to the best of our knowledge, we failed to find other examples of similar initiatives. Prevalence studies on worker populations are scarce. In the United States, a retrospective cohort study from the Military Health System Data Repository observed that approximately 4% of military active-duty women were diagnosed with PCOS between 2018 and 2022, and about 1% met the criteria for diagnosis every year [131]. Similar results were obtained from a cohort of military dependents [132]. In this occupational category, the incidence of ovarian dysfunction diagnosis, driven almost entirely by polycystic ovary syndrome, gradually increased from 32.0 cases per 10,000 person-years in 2014 to 60.3 cases per 10,000 person-years in 2023 [133]. The increase in PMOS cases involves the entire world population. Projections based on global trends in 1990–2021 indicate continued growth by 2050 [134,135,136]. The large increase in the global prevalence and incidence of PMOS over the last thirty years has resulted in a doubling of the years lived with disability by patients [137] and consequently in an increase in disability problems in the workplace. This phenomenon should have stimulated occupational studies to clarify the impact of this disease on productive activities and encourage the implementation of management measures, but to date this has not occurred.

A few studies have examined the role of occupational factors in PMOS etiopathogenesis. A Chinese case-control study on 366 patients with PCOS and 325 controls associated the syndrome and insulin resistance with occupational stress levels by logistic regression models, obtaining a low cumulative determination coefficient (R² = 0.22) [138]. Another Chinese study failed to observe a relationship between shift work and PCOS in a prospective cross-sectional study of 231 women, including healthcare workers recruited for an annual health screen. Nevertheless, women who indicated sleeping less than 6 h were more prone to report irregular menstrual cycle durations (OR = 2.1; 95% CI, 1.1 to 4.2), elevated fasting insulin concentrations (mean difference = 2.13; 95% CI, 0.27 to 3.99 mU/L) and increased likelihood of insulin resistance (OR = 2.58; CI, 1.16 to 5.76) [139]. The limited number of studies in the workplace is compensated for by epidemiological investigations that link this pathology to environmental factors. For example, a Chinese case-control study on 169 patients and 338 matched controls observed an association between PCOS and certain habits such as eating plastic-packaged food, eating contaminated fruit with pericarp, and drinking alcohol [140]. Another Chinese retrospective case-control study on 108 cases and 108 controls, after multivariate analyses, associated the syndrome with using disposable plastic cups for drinking as well as being exposed to cooking oil fumes and to indoor decorations [141]. A more recent retrospective case-control study on 178 PCOS patients and 206 controls from a Chinese tertiary hospital reported an association of outdoor particulate air pollution with the syndrome [142]. In contrast, a longitudinal register-based Danish cohort study including 21,619 residents during 380,000 person-years found no evidence of an association between environmental polychlorinated biphenyl pollution levels and incident PMOS cases [143]. A Swedish cohort study composed of 29,106 females who had resided in a municipality with perfluoroalkyl substances (PFAS)-contaminated water has demonstrated that exposure to high levels of PFAS in drinking water is associated with an increased risk of PCOS [144]. Endocrine disruptors and microplastics are among the factors most often associated with the disease [145,146,147]. Ecological studies suffer from an inevitable time lag between the release of new contaminants into the environment (e.g., micro- and nanoplastics, substitutes for bisphenol A and plasticizers, and flame retardants) and the availability of epidemiological data on populations [148]. Ecosystem pollution due to a complex set of endocrine disruptors appears to be the main cause of the global increase in PMOS.

A strength of this study is the development of an innovative PMOS case-finding program in the workplace. The project demonstrated the feasibility of identifying young women who had not previously sought primary care. The modest utilization of healthcare resources has been largely offset by the economic, productivity, and quality of life advantages that, according to the literature, may be associated with an early diagnosis of PMOS. Nevertheless, this study presents numerous limitations that represent a number of areas for improvement. Firstly, female workers who were deemed to be potentially affected by PMOS were invited to continue diagnostic tests under the National Health Service. This was the only viable option, since the activity was unfunded. However, if the research had been funded, the employer’s willingness to pay for the tests would definitely have accelerated the implementation time and would probably have decreased the number of people who failed to follow the doctor’s advice. Secondly, the decision to make use of a nutritional health promotion program to identify workers who might be suffering from eating or metabolic disorders associated with PMOS enabled us to reduce the number of in-depth interviews but excluded cases without nutritional or metabolic problems. Probably, a program involving all women of childbearing age would have detected a greater number of cases. Thirdly, consideration must be given to the fact that both the selection of the workers and the judgment resulting from the in-depth interviews followed subjective and therefore fallible criteria. However, having started to deal with the problem has made it clear to the doctor and the workers that PMOS is a syndrome that should not be overlooked. Fourth, the occupational physician had no control over the diagnostic and therapeutic pathways followed by each suspected patient. However, the action taken in the workplace was useful in establishing a channel of communication with general practitioners, endocrinology and gynecology specialists chosen by each patient. Finally, the study was conducted on a convenience sample, corresponding to workers examined in 2022 who were selected on the basis of nutritional and metabolic problems and were followed up in 2023. The data on the proportion of newly diagnosed PMOS and the clinical characteristics of the cases cannot therefore be extrapolated to other samples selected using different criteria. However, our study provides a structured interview model that can be applied in other work environments.

5. Conclusions

This study demonstrated that targeted PMOS case-finding, conducted during workplace medical examinations with minimal resource expenditure, enabled undiagnosed cases to be detected and referred for treatment. This is expected to substantially improve the quality of working life and the well-being of workers. Detection of the syndrome enables the health surveillance service to support female workers in their efforts to undertake proper physical activity and nutritional practices and also to monitor the evolution of metabolic, cardiovascular, and neuropsychiatric comorbidities.

We hope that this pilot study will arouse the interest of other health surveillance services and promote the disclosure of this syndrome, which, although not directly linked to occupational risks, has a significant impact on workers’ health and work ability.