Renuka Malik Dr Renuka Malik is working as a Professor and Consultant in ABVIMS &DR RML Hospital, a tertiary-level Central Government teaching hospital. She is an alumni of Lady Hardinge Medical College .Her areas of interest include laparoscopy, menopause and high-risk obstetrics.
Background Menopause is a hypoestrogenic state. Menopausal symptoms like hot flushes, depression, joint pains and urinary symptoms all correlate with falling estrogen levels.
Material and Methods Four hundred postmenopausal women who underwent natural menopause were included in the study conducted from Nov 2018 to March 2020. Surgical menopause, premature menopause and those on hormone replacement were excluded. Serum estradiol was measured and assessment of severity of menopausal symptoms was done using MRS questionnaire. MRS score of 0–4, 5–8, 9–15 and more than 16 were taken as none/minimal, mild, moderate and severe postmenopausal symptoms, respectively. Correlation between serum estradiol and symptoms was analyzed statistically.
Results Mean age of menopause in our study population was found to be 47.2 ± 3.96 years. Somatic symptoms were found maximum out of all 3 subscales in study population. Psychological subscale which included depression and mood changes was found to have the strongest correlation with serum estradiol level compared to other two subscales (somatic and genito-urinary).
Discussion Psychological symptoms, somatic symptoms and genitor urinary symptoms at menopause show correlation with falling estrogen levels. We found maximum correlation of psychological symptoms with low serum estradiol level.
Conclusion There is an inverse correlation of serum estradiol value with menopausal symptoms, with psychological symptoms (depression, anxiety, mood changes) showing highest correlation with low estrogen levels.
Keywords : Serum estradiol · Menopause · Menopausal symptoms · Menopause rating score · Menopause in Indian women
Menopause is a retrospective clinical diagnosis following 12 months of FMP (final menstrual period) [1]. Menopause is a hypoestrogenic state. Estrogen receptors are found all over human body brain, heart, skin, bones and urogenital system. Menopausal syndrome comprises of vasomotor symptoms, psychological symptoms and genito-urinary symptoms. These symptoms apart from hot flushes are also associated with normal aging process. Correlation between these symptoms and declining serum estradiol level is sought in this study.The study was carried out at A.V.I.M.S and Dr RML from November 2018 to March 2020. In total, 400 menopausal women attending gynecological OPD who had attained natural menopause were included in the study. Patients with surgical menopause, premature ovarian failure and patients on hormonal replacement therapy were excluded. Patient’s age at menopause, duration of menopause and comorbidities were noted.
Patients were given MRS questionnaire in English and Hindi depending upon their language proficiency, which was filled by the patient in the presence of the researcher. The postmenopausal symptoms were graded according to the severity. MRS consists of a list of 11 symptoms which are divided into 3 subscales—Somatic subscale (hot flashes, heart discomfort, sleep disorder, joint and muscular discomfort) corresponding to questions 1, 2, 3 and 11, respectively, Psychological subscale (depressive mood, irritability, anxiety, physical and mental exhaustion) corresponding to questions 4, 5, 6 and 7, respectively, and Urogenital subscale (sexual problems, bladder problems, dryness of vagina). Corresponding to questions 8, 9 and 10, respectively, patients graded their symptoms in a 5-point (0–4) Likert scale as none (0), mild (1), moderate (2), severe (3) and very severe as 4 (Table 1). Score were added and individual subscale and total menopausal score calculated and graded. The total score varied from 0 to 44. 0–4 was graded as none or minimal menopausalsymptoms, 5–8 as mild menopausal symptoms, 9–15 as moderate and 16–44 as severe postmenopausal symptoms. After assessment of symptoms detailed physical and gynecological examination was done, and 1 ml blood was withdrawn from median cubital vein for serum estradiol. Serum estradiol was measured using an direct immunoassay Ortho-Clinical Diagnostics’ Vitros assay, and results were expressed in units of pMol/L [pMol/L (pg/ml × 3.67)]. The laboratory reference value was below 141 pMol/L for menopausal patients. The severity of menopausal symptoms was then correlated with serum estradiol level.
Menopause is a hypoestrogenic manifestation of a variety of symptoms following cessation of ovarian function so distinct from aging, though a part of aging process. During reproductive years, estrogen synthesis begins in theca cells in ovary with androgen synthesis and ends with conversion of androgens to estrogens in granulosa cells by the enzyme aromatase. Estradiol is also produced in a number of extragonadal organs, including brain, fat, adrenal gland, skin. Blood vessels and bone have also been discovered to synthesize estradiol as they express aromatase activity. There are three major forms of physiological estrogens in females: estrone (E1), 17β-estradiol (E2) and estriol (E3). E1 and E2 are the 2 major biologically active estrogens in humans. A third bioactive E3 is the pregnancy estrogen produced by placenta but plays no significant role in non-pregnant. E2 is the major product from the whole biosynthesis process and is the most potent estrogen during the premenopausal period in a woman’s life, whereas E1 plays a larger role after menopause. E1 and E2 are mutually convertible, and E2 is 3–5 times more potent than E1. At menopause, the granulose cells become atretic and theca cells continue to synthesize androgens for some time which is converted to estrogens and extragonadal sites come into play. A major difference is that the tissues and cells of the extra-gonadal sites of estrogen synthesis are unable to synthesize C19 steroids but are able to convert circulating C19 steroids to estrogens using aromatase. This extragonadal synthesized estrogen is thought to act locally which limits its systemic effects [2]. There are three major forms of physiological estrogens in females: estrone (E1), 17β-estradiol (E2) and estriol (E3). Estrogens act through 2 types of their receptors: classical nuclear receptors (ERα and ERβ) and novel cell surface membrane receptors (GPR30 and ER-X). Estrogen receptors have been found in brain and periphery including adipose tissue, bone, kidney, blood vessels and skin [2, 3]. In reproductive years serum E2 value is 30–400 pg/mL, but after menopause, it falls below 30 pg/mol or 141 pmol/L (vitros). For hormone measurement at relatively low circulating concentrations as in menopause, traditional immunoassays such as ELISAs (enzyme-linked immunosorbent assay) commercial E2 assay suffer from cross-reactions and low reproducibility [4].
In western world, menopause occurs at a mean age of 51–52 years [5]. Menopause is earlier in Indian women as compared to western countries by 4–5 years. We found mean age of menopause in our study population was found to be 47.2 ± 3.96 years ranging from 46 to 50 years. As per Indian menopausal society, the average age of menopause in Indian women is 47.5 years. Other Indian studies have also found mean age of menopause was 48.9 years [6]. The most common menopausal symptom reported in our study was joint pain (67.25%). Joint pain, hot flushes, sleep disturbance and physical and mental exhaustion were the severe symptoms experienced by our study group. This finding was consistent with other Indian studies [6, 7]. Joint pains and sarcopenia are more troublesome than hot flushes in Indian women interfering with their day-to-day activities. It is another hall mark of menopause [8]. In our study, sexual problems were reported by (42.25%). Other studies have reported similar incidence from 12 to 45% [9].
Serum estradiol in postmenopausal women is less than 141 pMol/L, according to our laboratory reference values. The mean serum estradiol of study population was 77.23 ± 39.35 pMol/L with median of 78 pMol/L. The range of serum estradiol was from 5 to 256 pMol/L. We found incidence of hot flushes, and night sweats were found to be 53.5% in our study population. Hot flushes are more common and severe in western population, seen in 50–82% [9–11]. Asian studies have found similar lower incidence [6, 12]. In our study out of all 3 subscales of MRS, highest score rated, i.e., most severe symptoms were the somatic symptoms and then psychological symptoms followed by genito-urinary symptoms.
Declarations
Conflict of interest The authors declare that they have no conflict of interest statement.
Ethical approval Ethical clearance for the study was taken from hospital ethics committee with number-TP(MD/MS)(98/2018)/IEC/ 1931 (attached as supplementary file).
Informed Consent Written informed consent of all study subjects was taken.
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