EC Pharmacology and Toxicology

Menopause marks the cessation of menstruation due to the loss of follicular function [1,2]. Some women in this stage report several symptoms that prevent them from reaching deep sleep, reducing their quality of life, and triggering a depressive state, lousy mood, and memory loss [3-5]. It has been previously reported that such sleep disorders worsen with age; 9.2% of women between 40 - 49 years, 21.1% between 50 - 59 years, and 25.7% > of 60 years suffer from them [2,5].

During the late menopausal transition in women, annual hormone testing indicates a decrease in estradiol and an increase in follicle-stimulating hormone (FSH) [1]. The rise in FSH levels has been positively associated with sleeplessness, measured by polysomnography. The polysomnography [6] process has been useful in determining and defining the arousals in perimenopausal women after sleep onset [7]. Lowering FSH levels with estrogen and progesterone treatment (EPT) may be an option to decrease the arousals after sleep onset and the number of awakenings in women who report this sleep problem [8]. It has been demonstrated that estrogen therapy improves sleeping problems in postmenopausal women [2,8]. Moreover, Plamberger., et al. showed, in women, that both progestogen treatment and the luteal phase of the menstrual cycle increase fast sleep spindle density.

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2. Brown AMC and Gervais NJ. “Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan”. Endocrinology (2020): 161.
3. Baker FC., et al. “Insomnia in women approaching menopause: Beyond perception”. Psychoneuroendocrinology 60 (2015): 96-104.
4. Polo-Kantola P. “Sleep problems in midlife and beyond”. Maturitas3 (2011): 224-232.
5. Irwin MR. “Why sleep is important for health: a psychoneuroimmunology perspective”. Annuals Review Psychology 66 (2015): 143-172.
6. Rundo JV and Downey R 3^rd. "Polysomnography". Handbook of Clinical Neurology 160 (2019): 381-392.
7. De Zambotti M, Colrain IM and Baker FC. "Interaction between reproductive hormones and physiological sleep in women". Journal Clinical Endocrinology and Metabolism4 (2015): 1426-1433.
8. Silvestri R., et al. “Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders”. Maturitas 129 (2019): 30-39.
9. Plamberger CP., et al. “Impact of menstrual cycle phase and oral contraceptives on sleep and overnight memory consolidation”. The Journal of Sleep Research 30 (2021): e13239.
10. Lobo RA., et al. “A 17βEstradiol-Progesterone Oral Capsule for Vasomotor Symptoms in Postmenopausal Women: A Randomized Controlled Trial”. Obstetrics and Gynecology 132 (2018): 161-170.
11. Kagan R., et al. “Improvement in sleep outcomes with a 17β-estradiol-progesterone oral capsule (TX-001HR) for postmenopausal women”. Menopause 26 (2018): 622-628.
12. Smith MT and Wegener ST. “Measures of sleep: The Insomnia Severity Index, Medical Outcomes Study (MOS) Sleep Scale, Pittsburgh Sleep Diary (PSD), and Pittsburgh Sleep Quality Index (PSQI)”. Arthritis Care and Research 49 (2003): S184-S196.
13. Kaunitz AM., et al. “17β-estradiol/progesterone in a single, oral, softgel capsule (TX-001HR) significantly increased the number of vasomotor symptom-free days in the REPLENISH trial”. Menopause 27 (2020): 1382-1387.
14. Mirkin S., et al. “Relationship between vasomotor symptom improvements and quality of life and sleep outcomes in menopausal women treated with oral, combined 17β-estradiol/progesterone”. Menopause 26 (2019): 637-642.
15. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 25 (2018): 1362-1387.