Menopause is the physiological cessation of reproductive capacity in a woman’s life. Usually, it occurs between 45-55 years unless pathological conditions induce premature or early menopause (1).

Menopausal transition (also known as climacteric) starts with the onset of menstrual abnormalities and ends with the last menstrual period. Physiological changes during climacteric -mainly related to hormonal variations - may trigger a variety of menopausal symptoms that might last years in the postmenopausal period (2, 3).

Menopausal symptoms include psychological (depressive mood, irritability, anxiety, tiredness), somato-vegetative (hot flushes, palpitations, insomnia, muscle and joint pain), and urogenital (sexual problems, bladder problems, and vaginal dryness) disorders (1–3). Notably, several cohort studies have demonstrated an association between menopausal symptoms and lower quality of life (4–8).

In addition, hormonal changes during menopause contribute significantly to weight gain, increased visceral fat mass, and the development of abdominal obesity (3). Therefore, postmenopausal women may also present obesity-related metabolic disorders (i.e., insulin-resistance, dyslipidemia, and metabolic syndrome) that associate with an increased risk of type 2 diabetes, cardiovascular disease, and other chronic-degenerative diseases (9–11).

The Mediterranean diet (MD) is a healthy dietary pattern that has been associated with a reduced risk of cardiovascular events, morbidity and overall mortality, and the improvement of body weight, metabolic profile, and cognitive function (11–14).

MD is characterized by a wide variety of plant foods, such as vegetables, fruits, legumes, nuts, and whole-grain cereals, and the use of extra-virgin olive oil as the main source of fat (15). Therefore, MD provides low amounts of saturated fats in favor of unsaturated fats, and many bioactive compounds with anti- inflammatory and antioxidant activities (omega 3 fatty acids and vitamins, minerals, and phytochemicals, respectively) (15). More in detail, most of MD energy intake comes from carbohydrate (55%), close to 30% from fat, and the remaining part by protein (15%). Fats are mainly represented by 19% of monounsaturated fatty acids (MUFA), followed by saturated fatty acids (SFA, 9%) and polyunsaturated fatty acids (PUFA, 5%), and cholesterol is 300 mg/day (15).

Several studies suggested that MD might play a role in the reduction of body weight and menopausal symptoms in postmenopausal women by virtue of its dietary composition. In particular, a cross-sectional study in 481 postmenopausal women showed that a high adherence to the MD, evaluated by the Mediterranean Diet Score (MDS), was negatively associated with body weight, waist circumference, and waist-to-height ratio (16). Moreover, a cross-sectional study in 8.954 Spanish perimenopausal-post-menopausal women showed that high adherence to the MD was associated with a lower prevalence and risk of being overweight/obese (17).

As for menopausal symptoms, Herber-Gast and colleagues (18) investigated the relationship between MD and risk of vasomotor symptoms (hot flushes and night sweats) in the Australian Longitudinal Study on Women’s Health, a cohort study involving 6,040 postmenopausal women with a 9 year- follow-up. In this study a higher adherence to MD was inversely associated with vasomotor menopausal symptoms, thus suggesting that MD might be useful to prevent vasomotor menopausal symptoms.

Against this background, the aim of the present study was to investigate the impact of adherence to MD on the severity of menopausal symptoms in postmenopausal women with obesity. In addition, we explored the possible association between postmenopausal symptoms and the main foodstuffs characterizing MD.

A total of 100 postmenopausal women with obesity (BMI 35.0 ± 5.5 kg/m², mean age 57.2 ± 7.3) were included in the analyses. The main characteristics of the study participants (demographic, anthropometric and medical data, lifestyle habits) and the mean score of the interview questionnaires (PREDIMED and PSQI) were reported in Table 1 .

Seventy-five (65%) participants presented grade I obesity whereas women with grade II and grade III were 18 (18%) and 17 (17%), respectively.

WC was 107.4 ± 13 cm, HC was 120.3 ± 14.8, and WHR was 0.89 ± 0.06. As for lifestyle habits, 23 women (23%) were smokers, and most of the participants were sedentary 79 (79%). The prevalence of diseases was: 8% type 2 diabetes, 39% hypertension, and 39% dyslipidemia. Participants taking medications were 36% antihypertensive, 6% antidiabetic, 8% hypolipidemic medications, and 7% anticoagulant medications.

The mean PREDIMED score was 7.82 ± 1.7. Eight (8%) participants presented low adherence, 77 (77%) had average adherence, while 15 (15%) had high adherence. The mean PSQI score was 8.68 ± 3.6. Twenty-one participants (21%) were good sleepers, while 79 (79%) were poor sleepers.

Total MRS scores and the severity of symptoms are reported in Table 2 . The mean MRS score was 22.5 ± 8.5, with the following prevalence of the severity of symptoms: 11 women (11%) none-to-moderate symptoms, 12 (12%) marked symptoms, and 77 (77%) severe symptoms. Regarding the somatic and psychological symptoms, most of the participants were in the third class of symptoms severity (39% and 29%, respectively), whereas 52% of participants were in the first class of severity for urogenital symptoms. As for the specific menopausal symptom, the most frequent disorders were sleep problems (80%), depressive mood (79%), anxiety (79%), physical and mental exhaustion (79%), and joint and muscular discomfort (79%).

Table 3 reported the population’s characteristics stratified by severity of menopausal symptoms identified according to the MRS score. No significant differences were observed for age, BMI, obesity grade, other anthropometric measures (WC, HC, and WHR), lifestyle habits (smoking, alcohol, physical activity), and medical history (prevalence of diseases, medications, and menopause-related data). However, a significantly lower PREDIMED score we observed in the “marked symptoms” class than the “none-to-moderate symptoms” class (7.08 ± 1.2 vs. 9.50 ± 0.7, respectively; p=0.036). The “severe symptoms” class presented a lower PREDIMED score than the “none-to-moderate symptoms” class (7.83 ± 1.6 vs. 9.50 ± 0.7, respectively; p=0.181), although the difference did not reach the conventional level of statistical significance.

PSQI score was significantly lower in the “severe symptoms” class than in “marked symptoms” (p=0.012) and “none-to-moderate symptoms” (p=0.002) classes.

Correlation analysis was performed to assess the association of menopausal symptoms with PREDIMED items. The intake of legumes (≥3 times/week) was inversely correlated to the MRS score (r= -0.201, p=0.045). The intake of extra-virgin olive oil was inversely correlated with psychological symptoms (r: -0.230, p=0.021), mainly related to reduced depressive mood (r= -0.205, p=0.041). No other significant correlations with PREDIMED items and menopausal symptoms were observed.

The present study showed that the severity of menopausal symptoms (assessed by MRS) was inversely associated with the adherence to MD. In particular, women in the marked MRS class had a significantly lower adherence to MD than women in the none-to-moderate MRS class. Therefore, we investigated what food component characterizing MD was mostly involved in this association. The results showed that the intake of legumes and extra-virgin olive oil was associated with lower severity of total menopausal symptoms and psychological symptoms, respectively. Furthermore, women in the severe MRS class presented a lower sleep quality compared to other classes.

The association between menopausal symptoms and adherence to MD has been previously reported in two large cohort studies in postmenopausal women with overweight/obesity. Interestingly, a 2-years clinical trial in demonstrated that postmenopausal women with overweight/obesity (n=116, aged 56.6 ± 3.8 years, BMI 29.6 ± 3.8 kg/m²) advised a MD-resembling diet (low intake of meat, pastries, cakes, and sweets, while high intake of virgin olive oil, nuts, vegetables, legumes, and fruits) experienced an improvement of menopausal symptoms (32).

The present study added information about the specific components of MD that might explain the association with post-menopausal symptoms. Although no previous studies focused on the consumption of legumes intake and the severity of menopausal symptoms, two meta-analyses of randomized controlled trials (33, 34) reported an inverse association between post-menopausal symptoms and soy intake - known to be a legume. The mechanism behind this effect seems to be related to the activity of isoflavones. Indeed, isoflavones are biologically active compounds, with a chemical structure resembling estrogens. Therefore, they can bind estrogen-receptors thus positively influencing menopausal symptoms (35, 36). Dietary intake of isoflavones ranges from 5 to 80 mg/day in Asia, whereas in Western populations the reported daily intake is usually less than 3 mg/day (37). However, a study carried out in 14.029 individuals living in Southern Italy (38), with a strong Mediterranean gastronomic background, reported an isoflavone intake ranging 18-31 mg/day.

Regarding the use of extra-virgin olive oil, in this study women who consumed extra virgin olive oil experienced less psychological symptoms, in particular depressive mood.

Although this finding has not been observed in postmenopausal women, a 12-week nutritional trial carried out in 149 individuals with severe obesity (BMI > 35 Kg/m²) showed that daily consumption of extra virgin olive oil (52ml/day) significantly reduced depression and anxiety (39). In line with this, Foshati and colleagues demonstrated that the consumption of extra-virgin olive oil (25 ml/day for 7 weeks) significantly improved depressive symptoms in 73 patients with severe depression (40).

Although the psychological implications of diet are not completely clear (41, 42), pro-inflammatory foods such as those rich in saturated fats may induce the release of pro-inflammatory cytokines impairing the activity of the dopaminergic system, while the intake of monounsaturated fatty acids has shown to improve brain function (39).

Finally, as expected, participants in the severe MRS class presented a worsen sleep quality than other MRS classes. This finding is in line with a previous study carried out in 385 postmenopausal women aged <45 years investigating sleep quality by PSQI and its association with symptoms related to the menopausal period. In this study women who presented greater severity of menopausal symptoms reported greater impairment in sleep quality (43). The etiology of sleep disorders in menopausal women is still controversial. Some evidence suggested a role of the reduction of estrogens levels that can induce depression (44) and vasomotor symptoms (45). In addition, weight gain and particularly increased visceral adiposity can influence sleep quality through the secretion of cytokines or indirectly through obstructive sleep apnea that is frequently in individuals with severe obesity (46–48).

Although no correlation was found between sleep disorders and adherence to MD, nutrition might play a role in the modulation of sleep quality. Indeed, the intake of phytoestrogens has been associated with a reduction of the frequency of insomnia (49). Moreover, a high intake of omega-3 has been reported to decrease depression and anxiety which could contribute to improve sleep quality (50).

Nevertheless, we can not exclude the possibility that sleep disorders would worse the menopausal symptoms, at least the psychological aspects.

The present study had both strengths and limitations. It included a relatively large sample of postmenopausal women for exploring associations between MD and menopausal symptoms. However, it was a convenience sample, as participants were consecutively recruited from women attending the Outpatient Clinic of the Unit of Endocrinology, Department of Clinical Medicine and Surgery, University of Naples “Federico II”. In addition, the cross-sectional design of the study did not allow for cause-effect conclusions. Finally, all questionnaires used in this study were translated in Italian from the English version with no forward-backward translation method to guarantee the conceptual equivalence (51). Nevertheless, the participants were interviewed by expert operators thus increasing the reliability of the collected data.

In conclusion, in the present study, the adherence to MD was associated to lower severity of menopausal symptoms in women with obesity. Notably, legume consumption was associated with lower menopausal symptoms severity, and extra virgin olive oil was associated with a reduction in psychological symptoms. These findings highlight the importance of the MD as an ideal nutritional strategy in the management of menopause.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by University of Naples Federico II Ethics Committee. The patients/participants provided their written informed consent to participate in this study.

The authors’ responsibilities were as follows CV, LB, and GM: were responsible for the concept and design of the study, interpreted data and drafted the manuscript. CV, LB, and RR: conducted statistical analyses. RR, LV, GA, AD, and RA: collected data. AC, SS, and GM: provided a critical review of the manuscript. All authors contributed to and approved the final version of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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