- Open Access
Vitamin D levels and menopause-related symptoms in postmenopausal women
Middle East Fertility Society Journal volume 27, Article number: 29 (2022)
Menopause is an important period in women’s life. It is characterized by many symptoms that affect women’s quality of life. This study aimed to the evaluation of the relation between vitamin D levels and menopause-related symptoms.
Vitamin D insufficiency was noted in 52.4% of the studied population. There was no statistically significant difference in any of the menopausal rating scale dimensions, psychological symptoms (p = 0.16), somato-vegetative symptoms (p = 0.45), or urogenital symptoms (p = 0.59), between vitamin D sufficient and insufficient groups. The severity of the menopausal symptoms was affected by the presence of medical illness (p < 0.001).
Vitamin D deficiency is an alarming issue among postmenopausal women. It was not associated with menopause-related symptoms.
Menopause means the cessation of menstruation and typically occurs at the age of 45–55 years with a mean age of about 51 years. Women are said to be postmenopausal when menstruation has ceased for 6 to 12 months and blood serum levels of follicle-stimulating hormone (FSH) increase to at least 49 IU/L . Many women experience menopause-related symptoms long after the final menstrual period. For example, women often experience hot flushes 4–10 years postmenopause [2,3,4]. Many also have mood disturbances, although the link with menopause is less clear [2, 5]. These symptoms can be severe enough to negatively impact the quality of life, work performance, and personal relationships [6, 7]. Recognizing the possible mechanisms underlying menopause-related symptoms help in the development of new therapeutic strategies.
Calcium balance studies have shown that calcium absorption declines with menopause. 25-Hydroxyvitamin D [25(OH) D] serves the purpose of calcium absorption and appears to be hormonally sensitive. Also, some of the symptoms associated with vitamin D deficiency, such as mood disturbance and musculoskeletal complaints , are similar to symptoms women may experience during the transition through menopause . The primary aim of this study was to explore if there is any association between vitamin D status and the severity of menopause-related symptoms.
This cross-sectional study was conducted in the obstetrics and Gynecology Department of Suez Canal University Hospital. Postmenopausal women were divided into two groups regarding their levels of vitamin D: insufficient and normal (sufficient). The first group with insufficient serum 25(OH) D concentrations (i.e., ≥ 20 to < 30 ng/mL) (n = 88) and 2nd group with sufficient vitamin D levels (n = 80) . Women were recruited according to inclusion and exclusion criteria. Inclusion criteria were (a) women aged 50–70 years, (b) not taking hormonal therapy, and (c) reported menopausal symptoms. Exclusion criteria were (a) women already participating in a diet or exercise intervention, (b) history of bariatric surgery, (c) history of hysterectomy/oophorectomy, (d) women using medications known to impact hot flushes and/or weight (hormone therapy, oral contraceptives, gabapentin, selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors (SSRI/SNRIs), selective estrogen receptor modulators (SERMS), clonidine, antipsychotics, steroids, weight loss medications, chemotherapy), (e) women with possible medical conditions associated with vitamin D deficiency (following a malabsorption diet, colitis, pancreatic disease, current gall bladder problems, and liver disease), and (f) women with conditions that would influence vitamin D levels (high blood calcium or incident cancer).
Eligible women were evaluated thoroughly by proper history taking including any history of medical illness (diabetes, hypertension, and thyroid disease). Women were asked to complete the menopause rating scale. Women were interviewed in a private room. A researcher was available for help.
The severity of symptoms was classified as mild, moderate, and severe by the menopause rating scale (MRS). The scale consists of 11 symptoms in 3 domains:
Somato-vegetative: including vasomotor symptoms (hot flushes, heart discomfort, sleep problems) and musculoskeletal symptoms (joint and muscular discomfort) (domain scores 0–16)
Psychological symptoms (depressed mood, irritability, anxiety, physical, and mental exhaustion) (domain scores 0–16)
Urogenital symptoms (sexual problems, bladder problems, and vaginal dryness) (domain scores 0–12). Each symptom is scored from none (scored as 0) to very severe (score as 4), giving a score range from 0 to 44. Summation scores for severity were classified as  Table 1:
All participants provided a 12-h fasting of a 5-mL sample of the blood, which was processed within 1 h of collection by centrifugation, and serum was collected and stored at − 70 ℃. Participants were instructed to refrain from alcohol (48 h) and vigorous exercise (24 h) before clinic appointments. The relation between vitamin D levels and menopausal symptoms was evaluated.
The collected data was revised, coded, tabulated, and introduced to a PC using the Statistical Package for Social Science (SPSS 15.0.1 for windows; SPSS Inc, Chicago, IL, 2001). Data were presented as the mean and standard deviation (± SD) for quantitative parametric data, and median and interquartile range for quantitative nonparametric data. Frequency and percentage were used for presenting qualitative data. Suitable analysis was done according to the type of data obtained. Student T test or Mann–Whitney test was used to analyze quantitative data while chi-square test and Fisher’s exact test were used to analyze qualitative data: P value: level of significance, P > 0.05: non-significant (NS), P < 0.05: significant (S), and P < 0.01: highly significant (HS).
Vitamin D insufficiency was noted in 52.4% of the studied population. Table 2 showed that there was no statistically significant difference between vitamin D sufficient and insufficient groups in any of the patients’ baseline characteristics (P > 0.05).
There was no statistically significant difference in the mean score of each item of the MRS between women with sufficient and insufficient vitamin D levels but for feeling anxious, where higher scores were reported among those with sufficient vitamin D levels (P value 0.039). Joint and muscular discomfort and feeling nervous and irritable had the highest scores among the symptoms forming the menopausal rating scale (MRS) in both groups (Table 3).
There was no statistically significant difference in any of the menopausal rating scale dimensions, psychological symptoms (P = 0.12), somato-vegetative symptoms (P = 0.66), or urogenital symptoms (P = 0.63), between vitamin D sufficient and insufficient groups (Table 4).
There was no statistically significant difference in the severity of menopausal symptoms among groups with normal and insufficient vitamin D levels. There were nine patients with mild menopausal symptoms with insufficient and sufficient vitamin D levels. There were 30 27 patients with moderate menopausal symptoms with insufficient and sufficient vitamin D levels, respectively. There were 49 and 44 patients with severe menopausal symptoms with insufficient and sufficient vitamin D levels, respectively (P value 0.97).
In Table 5, we used a multivariable linear regression analysis to assess the predictor of severity of menopausal symptoms. We found that the best-fitting predictor for the severity of menopausal symptoms score was the presence of medical illness (P < 0.001). To illustrate, there is an increase in the odds of having severe menopausal symptoms in females who suffer medical illness by 41% more than those who do not have any medical illness, OR = 1.41 (3.039–7.461) (P < 0.001).
About 52.4% of the study subjects suffered from vitamin D insufficiency. A study conducted in India showed that vitamin D deficiency and insufficiency were prevalent among 70% and 23% of postmenopausal women, respectively . Another study reported that 52.37% of postmenopausal women had vitamin D deficiency. This would be rendered to the reduced capacity of the aging skin to effectively synthesize vitamin D . Also, a paradox exists in countries with a low-sun incidence, when compared to countries with a higher solar incidence, such as those of Mediterranean Europe. In the Middle East (lower latitudes), there is a high prevalence of vitamin D deficiency, which can be explained by the habitual use of clothing covering almost the entire body .
Feeling anxious was significantly elevated among women with sufficient vitamin D levels. Another study reported a significant association between anxiety and vitamin D levels; however, their studied population had insufficient vitamin D . An earlier one declined an association between vitamin D levels and anxiety . Conflicting results were reported regarding the association between vitamin D and anxiety. Some studies confirmed a positive association [17, 18] while others declined this point [19, 20]. However, these studies targeted different populations (patients with rheumatoid arthritis and children and adolescents on dialysis, and pregnant women). Vitamin D has a neuroprotective effect through inhibition of oxidative damage of the brain tissue . Additionally, decreased estrogen level affects CNS function through impaired synaptic processing and electrical excitability leading to anxiety .
Joint and muscular discomfort and irritability had the highest score among menopausal women. This agreed with previous results reporting joint pain and irritability among 90.3% and 84.9% of postmenopausal women . Another one reported joint and muscle pain as the most prevalent symptom among menopausal women (87%) . This was rendered to estrogen deficiency which might be related to the musculoskeletal system symptoms . Variable results would be rendered to different social, cultural, and environmental characters of the studied populations .
There was no statistically significant difference in the severity of menopausal symptoms between vitamin D sufficient and insufficient groups (P = 0.97). This agreed with the results reported by a previous study , although they recruited women with an increased average of age (66 years), increased duration of menopausal years (16 years postmenopause), and discouraged women with severe symptoms from participating in the study. However, another study reported lower vitamin D levels among women with greater menopausal symptoms especially vasomotor symptoms . This was rendered to their recruitment of breast cancer survivors on aromatase inhibitors. Another contradictory finding was reported . This contradiction would be explained by their inclusion of women with vitamin D deficiency while the current study did not. Additionally, they used different reference ranges than those reported in this study.
Vitamin D levels had no role in the prediction of the severity of menopausal symptoms together with other patient-related factors, but for medical illness (P < 0.001). This was in accordance with a previously published study , while contradictory results were reported where vitamin D levels were significantly associated with anxiety levels irrespective of age and depression levels . Compelling evidence supports the role of vitamin D in the developing brain as well as in the adult brain function. The vitamin D receptors and the biosynthetic machinery for the hydroxylation of vitamin D have been found, in neurons, glial cells, and the pituitary gland. Thus, neurological and psychological actions of vitamin D have been claimed . Additionally, another study reported that chronic diseases were related to the increased severity of menopausal symptoms [10, 30]. This would be rendered to the addition of symptoms related to these illnesses.
Strength and limitations
We recruited women with a relatively short duration of menopause. Also, women with severe symptoms were recruited. This study has some limitations. We recruited a small number of participants. This was a hospital-based study limiting the generalizability of the results. Patients with vitamin D deficiency were not included.
Vitamin D deficiency is an alarming issue among postmenopausal women; however, it was not associated with the severity of menopausal symptoms. Egypt being a Middle East country receives plenty of sunshine but at the same time exhibits rising vitamin D deficiency as Egypt embraces diversity in cultural practices and regional differences along with a distinct dietary pattern.
Availability of data and materials
- 25(OH) D:
Selective serotonin reuptake inhibitors
Selective norepinephrine reuptake inhibitors
Selective estrogen receptor modulators
Menopause rating scale
Central nervous system
Furness S, Roberts H, Marjoribanks J, Lethaby A (2012) Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst Rev 2012(8):CD000402
Simon JA, Reape KZ (2009) Understanding the menopausal experiences of professional women. Menopause 16(1):73–76
Freeman EW, Guthrie KA, Caan B et al (2011) Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA 305(3):267–274
Col NF, Guthrie JR, Politi M, Dennerstein L (2009) Duration of vasomotor symptoms in middle-aged women: a longitudinal study. Menopause 16(3):453–457
National Institutes of Health State-of-the-Science Conference statement (2005) Management of menopause-related symptoms. Ann Intern Med 142(12 Pt 1):1003–1013
Geukes M, van Aalst MP, Nauta MC, Oosterhof H (2012) The impact of menopausal symptoms on work ability. Menopause 19(3):278–282
Sarrel PM (2012) Women, work, and menopause. Menopause 19(3):250–252
Arvold DS, Odean MJ, Dornfeld MP et al (2009) Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Endocr Pract 15(3):203–212
Brunner RL, Aragaki A, Barnabei V et al (2010) Menopausal symptom experience before and after stopping estrogen therapy in the Women’s Health Initiative randomized, placebo-controlled trial. Menopause 17(5):946–54
Askin M, Koc EM, Soyoz M, Aksun S, Aydogmus S, Sozmen K (2019) Relationship between postmenopausal vitamin D level, menopausal symptoms and sexual functions. J Coll Physicians Surg Pak 29(9):823–827
Heinemann K et al (2004) Menopause rating scale (MRS): a methodological review. Health Qual Life Outcomes 2:45
Holick MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80(6 Suppl):1678S-S1688
Kalra S, Kalra B, Khandelwal SK (2011) Vitamin D deficiency in postmenopausal women in Haryana. World J Life Sci and Medical Research 1(11):1–5
Bandeira F, Griz L, Dreyer P, Eufrazino C, Bandeira C, Freese E (2006) Vitamin D deficiency: a global perspective. Arq Bras Endocrinol Metab 50(4):640–646
Martino G, Catalano A, Bellone F, Sardella A, Lasco C, Caprì T, Morabito N (2018) Vitamin D status is associated with anxiety levels in postmenopausal women evaluated for osteoporosis. Mediterr J Clin Psychol 6(1)
Armstrong DJ, Meenagh GK, Bickle I, Lee ASH, Curran ES, Finch MB (2007) Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol 26(4):551–554
Pu D, Luo J, Wang Y, Ju B, Lv X, Fan P et al (2018) Prevalence of depression and anxiety in rheumatoid arthritis patients and their associations with serum vitamin D level. Clin Rheumatol 37(1):179–184
Han B, Zhu FX, Yu HF, Liu S, Zhou JL (2018) Low serum levels of vitamin D are associated with anxiety in children and adolescents with dialysis. Sci Rep 8(1):5956
Huang JY, Arnold D, Qiu CF, Miller RS, Williams MA, Enquobahrie DA (2014) Association of serum vitamin D with symptoms of depression and anxiety in early pregnancy. J Women’s Health 23(7):588–595
Bossola M, Ciciarelli C, Di Stasio E, Conte GL, Vulpio C, Luciani G et al (2010) Correlates of symptoms of depression and anxiety in chronic hemodialysis patients. Gen Hosp Psychiatry 32(2):125–131
Jamali N, Sorenson CM, Sheibani N (2018) Vitamin D and regulation of vascular cell function. Am J Physiol Heart Circ Physiol 314(4):H753–H765. https://doi.org/10.1152/ajpheart.00319.2017 (Epub 2017 Dec 22. PMID: 29351464; PMCID: PMC5966766)
Thapa R, Yang Y (2020) Menopausal symptoms and related factors among Cambodian women. Women Health 60(4):396–411
Khatoon F, Sinha P, Shahid S, Gupta U (2018) Assessment of menopausal symptoms using modified menopause rating scale (MRS) in women of Northern India. Int J Reprod Contracept Obstet Gynecol 7(3):947–951
Magliano M (2010) Menopausal arthralgia: fact or fiction. Maturitas 67(1):29–33. https://doi.org/10.1016/j.maturitas.2010.04.009
Yanikkerem E, Koltan SO, Tamay AG, Dikayak S (2012) Relationship between women’s attitude towards menopause and quality of life. Climacteric 15:552–562
LeBlanc ES, Desai M, Perrin N et al (2014) Vitamin D levels and menopause-related symptoms. Menopause 21(11):1197–1203. https://doi.org/10.1097/GME.0000000000000238 (New York, N.Y.)
Khan QJ, Reddy PS, Kimler BF et al (2010) Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat 119(1):111–118
Martino G, Catalano A, Bellone F, Sardella A, Lasco C, Caprì T, Langher V, Caputo A et al (2018) Vitamin D status is associated with anxiety levels in postmenopausal women evaluated for osteoporosis. MJCP 6(1):1–16
Buell JS, Dawson-Hughes B (2008) Vitamin D and neurocognitive dysfunction: preventing “D”ecline? Mol Aspects Med 29(6):415–422
Van Schoor NM, Lips P (2011) Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 25:671–680
Ethics approval and consent to participate
All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was conducted after the approval of our research ethics committee. Informed consent was obtained from all participants before recruitment.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Hakim, N.H., Mohamed, M.L., El-Biely, M.M. et al. Vitamin D levels and menopause-related symptoms in postmenopausal women. Middle East Fertil Soc J 27, 29 (2022). https://doi.org/10.1186/s43043-022-00120-8
- Vitamin D