Peri-menopause is defined as the time “around menopause” or the natural transition into menopause. The peri-menopausal transition varies in time length for different women (usually ranging between 2-10 years) and can often be a highly symptomatic time in a woman’s life. Common symptoms of peri-menopause include irregular cycles, vasomotor symptoms, insomnia, mood changes including an increase in anxiety and depressive symptoms, genitourinary issues, changes in sexual function, loss of bone mass/density and increase in cholesterol levels (1). Peri-menopause is also a time where many women experience unexplained weight gain and/or a resistance to losing weight. In order to best understand how to support the body and mind through a smoother transition into menopause, it is crucial to understand the four stages of peri-menopause and the hormonal changes that occur at each stage.
Stage 1: early peri-menopause
This stage is marked by a decrease in progesterone levels. During stage 1, the menstrual cycle is still regular however over time ovarian reserves diminish and oocyte quality declines. This leads to a decrease in progesterone production and increasingly symptomatic cycles. It is also common to experience more sporadic anovulatory cycles in this phase (no ovulation). Low progesterone can manifest differently in women but often includes a shortening of the luteal phase (the phase of the menstrual cycle between ovulation and the next period), increased pre-menstrual spotting (3+ days) and heavier periods. In the case of sporadic anovulation, menstrual bleeding occurs either at the regular time, is delayed by approximately 2 weeks, or at the time following the next ovulation. (To understand the difference between periods and inter-menstrual bleeding please read this article here). Other symptoms associated with low progesterone include a loss of resilience and patience, feelings of overwhelm, anxiety, trouble sleeping, increase in pre-menstrual headaches/migraines and heart palpitations (10)(11).
Stage 2: early menopause transition
This stage is marked by wildly fluctuating hormone levels and irregular menstrual cycles. As the pituitary gland in the brain detects decreasing levels of progesterone as characterised by stage 1, compensatory mechanisms kick in to try and stabilise hormone production and extend fertility as much as possible. The result is a rise in follicle stimulating hormone (FSH) levels. FSH attempts to stimulate the ovaries into releasing more eggs and therefore produce more estrogen and progesterone. An increase in FSH can result in up to three times higher levels of estrogen in any given menstrual cycle (2). Fluctuating estrogen levels, combined with declining progesterone levels leads to irregular and often shorter menstrual cycles. At this stage some women experience the arrival of their period every 2-3 weeks instead of monthly. High estrogen without adequate progesterone also leads to heavy menstrual bleeding and contributes to “abnormal uterine bleeding” or “menometrorrhagia.” This type of irregular, unpredictable, prolonged and heavy bleeding can occur in over 24% of peri-menopausal women (due to under- reporting these numbers are likely even higher) (7). While not all women experience shorter cycles or abnormal uterine bleeding, most women in the second stage of peri-menopause will experience changes in the regularity of their menstrual cycles by at least 6-7 days. During the second stage of peri-menopause, a sudden rise in estrogen is often followed by a large drop in estrogen leading to oscillating symptoms of high and low estrogen. Symptoms can range from heavy periods, breast tenderness, anxiety and irritability in one cycle to hot flushes, night sweats, vaginal dryness, brain fog and depression in another.
Stage 3: late menopause transition
This stage is marked by an overall decrease in both estrogen and progesterone and delayed ovulation. Cycles prolong to 60+ days and the length between menstrual cycles extends. During this stage many symptoms of high estrogen are resolved and replaced with low estrogen symptoms such as vaginal dryness, vasomotor symptoms such as hot flushes and night sweats, depression, brain fog, changes in sexual function and increase in genitourinary problems eg. urinary tract infections, bladder infections or vaginal infections. Low estrogen and progesterone also contribute to loss of bone and muscle mass, thereby slowing metabolic function and greatly increasing the risk of osteopenia, osteoporosis and weight gain. Low estrogen interferes with the normal functioning of the liver and gall bladder leading to higher cholesterol levels and increase risk of gall bladder stones. (To read more about changes to the liver and gall bladder in peri-menopause, please read my article here). Estrogen is directly involved in regulating insulin sensitivity, energy expenditure and fat accumulation (3). A loss of estrogen is therefore greatly associated with menopausal weight gain and an increase in chronic health conditions such as heart disease and diabetes. In addition, a loss of estrogen has recently been discovered to have profound effects on the brain. While a loss of estrogen has shown mixed results on cognitive performance, estrogen loss can affect memory retention in the short term and is associated with an increase likelihood of alzheimers disease later in life (8)(9).
Stage 4: late peri-menopause
This stage is defined as the time between the last period and reaching menopause/post menopause. Menopause is considered to have occurred 12 months after the last menstrual period. In this time, estrogen and progesterone are no longer falling and remain low at baseline. This means that many peri-menopausal symptoms start to diminish, although some symptoms such as hot flushes can last for 10 + years after menopause. While some women remain symptomatic, quality of life begins to improve and many women report better wellbeing post menopause than at any other stage in life. Testosterone is the last hormone of the menstrual cycle to decline in menopause. This occurs mostly because testosterone drops slowly and gradually over time while both estrogen and progesterone plummet during the peri-menopausal transition. This can sometimes lead to relative testosterone/androgen excess in relation to estrogen (5). While many of the symptoms associated with androgen excess are temporary and mild, higher relative testosterone can influence fat accumulation, weight gain and insulin resistance further influencing weight gain and diabetes risk. In some women, testosterone may become excessively low over time contributing to a worsening of hypoactive sexual desire disorder (low libido) (6). While symptoms are easing, estrogen remains low and therefore the risks associated with low estrogen still apply. This includes a loss of bone density/mass, metabolic change/insulin resistance, increased cholesterol and increase risk of chronic disease.
Navigating the many changes of peri-menopause requires a thorough understanding of the hormonal shifts that occur at each of the four stages of peri-menopause and beyond. Menstrual cycles become irregular due to changes in the timing of ovulation. It is therefore beneficial for most women to learn how to correctly monitor ovulation through the fertility awareness method or menstrual cycle tracking. Learning when ovulation occurs can help women identify which stage of perimenopause they are in and provide foreknowledge for the arrival of the next period/cycle. This can help make the perimenopause transition more predictable and therefore less disruptive to life. Having an understanding of the stages of perimenopause can also assist women in making the necessary dietary, lifestyle and/or medical changes to support their well being in a highly transitional time in life.
References:
1.Duralde, E. R., Sobel, T. H., & Manson, J. E. (2023). Management of perimenopausal and menopausal symptoms. BMJ (Clinical research ed.), 382, e072612. https://doi.org/10.1136/bmj-2022-072612
2. Prior J. C. (2011). Progesterone for Symptomatic Perimenopause Treatment – Progesterone politics, physiology and potential for perimenopause. Facts, views & vision in ObGyn, 3(2), 109–120.
3. Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013). The role of estrogens in control of energy balance and glucose homeostasis. Endocrine reviews, 34(3), 309–338. https://doi.org/10.1210/er.2012-1055
4. Janssen, I., Powell, L. H., Kazlauskaite, R., & Dugan, S. A. (2010). Testosterone and visceral fat in midlife women: the Study of Women’s Health Across the Nation (SWAN) fat patterning study. Obesity (Silver Spring, Md.), 18(3), 604–610. https://doi.org/10.1038/oby.2009.251
5. Zaman, A., & Rothman, M. S. (2021). Postmenopausal Hyperandrogenism: Evaluation and Treatment Strategies. Endocrinology and metabolism clinics of North America, 50(1), 97–111. https://doi.org/10.1016/j.ecl.2020.12.002
6. Parish, S. J., & Kling, J. M. (2023). Testosterone use for hypoactive sexual desire disorder in postmenopausal women. Menopause (New York, N.Y.), 30(7), 781–783. https://doi.org/10.1097/GME.0000000000002190
7. Donnez, J. (2011). Menometrorrhagia during the premenopause: an overview. Gynecological Endocrinology, 27(sup1), 1114–1119. https://doi.org/10.3109/09513590.2012.637341
8. Briceno Silva, G., Arvelaez Pascucci, J., Karim, H., Kaur, G., Olivas Lerma, R., Mann, A. K., Gnanasekaran, S., & Thomas Garcia, K. D. (2024). Influence of the Onset of Menopause on the Risk of Developing Alzheimer’s Disease. Cureus, 16(9), e69124. https://doi.org/10.7759/cureus.69124
9. Conde, D. M., Verdade, R. C., Valadares, A. L. R., Mella, L. F. B., Pedro, A. O., & Costa-Paiva, L. (2021). Menopause and cognitive impairment: A narrative review of current knowledge. World journal of psychiatry, 11(8), 412–428. https://doi.org/10.5498/wjp.v11.i8.412
10. Carpenter, J. S., Cortés, Y. I., Tisdale, J. E., Sheng, Y., Jackson, E. A., Barinas-Mitchell, E., & Thurston, R. C. (2023). Palpitations across the menopause transition in SWAN: trajectories, characteristics, and associations with subclinical cardiovascular disease. Menopause (New York, N.Y.), 30(1), 18–27. https://doi.org/10.1097/GME.0000000000002082
11. Pavlović J. M. (2018). Evaluation and management of migraine in midlife women. Menopause (New York, N.Y.), 25(8), 927–929. https://doi.org/10.1097/GME.0000000000001104
