Steroid Hormone Secretion Over the Course of the Perimenopause: Findings From the Swiss Perimenopause Study

Abstract

Background: Perimenopause is characterized by a decline in the steroid hormones, estradiol, and progesterone. By contrast, the steroid hormone cortisol, a marker of the hypothalamic–pituitary–adrenal (HPA) axis, increases. Recent longitudinal studies reported fluctuations in steroid hormone levels during perimenopause, and even increases in estradiol levels. To understand these confounding results, it is necessary to conduct a longitudinal, highly standardized assessment of steroid hormone secretion patterns in perimenopausal women.Methods: This longitudinal study investigated 127 perimenopausal women aged 40–56 years for 13 months. Estradiol, progesterone, and cortisol were assessed using saliva samples, which were collected for two (during months 2 and 12 for estradiol and progesterone) or three (during months 2, 7, and 12 for cortisol) non-consecutive months over the course of the study. A total of 14 saliva samples per participant were analyzed to investigate the courses of estradiol and progesterone. Cortisol awakening response and fluctuations of cortisol throughout the day were measured using a total of 11 saliva samples per participant (on awakening, +30 min, +60 min, at 12:00 p.m., and before going to bed) for months 2, 7, and 12.Results: Multilevel analyses revealed variance in intercept and slope across participants for estradiol [intercept: SD = 5.16 (95% CI: 4.28, 6.21), slope: SD = 0.50 (95% CI: 0.39, 0.64)], progesterone [intercept: SD = 34.77 (95% CI: 25.55, 47.31), slope: SD = 4.17 (95% CI: 2.91, 5.99)], and cortisol (intercept: SD = 0.18 (95% CI: 0.14, 0.23), slope: SD = 0.02 (95% CI: 0.01, 0.02)]. Time predicted cortisol levels [b = −0.02, t(979) = −6.63, p < 0.0001]. Perimenopausal status (early vs. late) did not predict estradiol [b = −0.36, t(1608) = −0.84, p = 0.400], progesterone [b = −4.55, t(1723) = −0.87, p = 0.385], or cortisol [b = 0.01, t(1124) = 0.61, p = 0.542] scores over time.Discussion: Our results are consistent with previous findings emphasizing highly individual fluctuations of estradiol and progesterone levels during perimenopause. However, our findings do not suggest a continuous decline during the observed transition phase, implying relatively stable periods of fluctuating hormone levels. Furthermore, given the lack of significant group differences, it may not be necessary to differentiate between early and late perimenopause from the standpoint of hormonal progression.

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“…27 Perimenopause is a special and inevitable period which represents the final reproductive transition stage in a woman's life. 28,29 Women in the perimenopausal period have increased prevalence of depressive symptoms compared with women in the premenopausal period. 28 With the influence of breast cancer and surgery on mental health, perimenopausal women undergoing modified radical mastectomy are more prone to mental problems.…”

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“…On the other hand, physical parameters, such as middle-Age, raised HR (evident by palpitations due to increased vasomotor response to hormonal imbalance [33]), BMI (gained weight towards obesity [34]), high systolic and diastolic BP (as essential hypertension settles in the body as age advances [35]), irregular synthesis and secretion of estradiol and progesterone (which is a measure of the hypothalamus-pituitaryovarian axis [36]), TSH (often is elevated to compensate for the increased demand of thyroxin in the body [37]), HbA1c (rises as type-2 diabetes settles down in the body [38]), and cortisol (a measure of the hypothalamus-pituitary-adrenal axis is often elevated due to the increment of stress [39]) have direct or indirect relationships with the perimenopause stage in the women's life.…”

Climatério

“…Portanto, ainda que haja redução na secreção hormonal nos extremos do período menopausal, essa flutuação não previsível torna o uso de FSH, E2, inibinas e cortisol menos sensíveis, principalmente, na fase intermediária (GRUB et al, 2021).…”