What are early and pre-menopause?

What are early and pre-menopause?

Menopause is defined by the World Health Organization (WHO) as the permanent cessation of menstruation that happens due to the loss of ovarian follicular activity (1). In most women, menopause happens between 45 and 50 years of age, with an average age of 51 in western countries (2). Early natural menopause is defined as the menopause that occurs between the ages of 40 and 45 years, and it affects approximately 5% of women. Meanwhile, premature menopause is the one that happens before 40 years old, and it happens to around 1% of all women (3).

Amenorrhoea for 4 months or more (absence of menstruation), high levels in serum of follicle stimulating hormone (FSH), and low estradiol levels are characteristics of this premature ovarian insufficiency (POI) (1).

POI is related to health problems due to the low levels of estrogen. Some of these health issues are: low bone mineral density, infertility, mood disorders, increased risk of cardiovascular disease, diabetes and dry eye syndrome, as well as menopausal symptoms like hot flashes, insomnia, decreased sexual desire, and vaginal dryness (4).

The reason why POI occurs can be due to genetic disorders, secondary to chemotherapy, radiation or surgery, or it appears spontaneously (4). The most common cause of premature or early menopause is the surgery where the ovaries are removed (3).

Is important to know that POI is different from decreased ovarian reserve (DOR), which are patients with regular menses, but whose response to ovarian stimulation or fertility is reduced (1). Nowadays, the evaluation of ovarian aging is made by measuring the levels of hormones in serum (e.g FSH and anti-Müllerian hormone), assessing the antral follicle count (AFC), doing an ultrasonography, all of these together with the age.

**What are the recommendations in case of early or premature menopause? **

Medical societies recommend hormone replacement therapy until the age of natural menopause (3,4). For bone health weight-bearing exercises are recommended, as well as muscle strengthening, stop smoking, avoiding excess alcohol intake, and a daily intake of 1200 mg of calcium and 600-1000 IU of vitamin D from food and/or supplements. Mental health is as important as physical health, that’s why psychological support is also recommended in women with early or premature menopuase due to the changes in self-image, sexual dysfunction and loss of fertility (3).

There are novel therapies that could help to restore ovarian function, however, they are still in their experimental stages. In vitro activation, mitochondrial activation, stem cell and exosomes therapy are examples of these new therapies (5).

Although pregnancies have occurred in women with POI, so far it is still not possible to determine the probabilities of spontaneous remission. For this reason, women that want to have a baby are recommended to go through assisted reproductive techniques with oocyte donation and in vitro fertilization (1).

**References: **

1.Hernández-Angeles, C., & Castelo-Branco, C. (2016). Early menopause: A hazard to a woman's health. The Indian journal of medical research, 143(4), 420–427. https://doi.org/10.4103/0971-5916.184283 2.Mishra, G. D., Pandeya, N., Dobson, A. J., Chung, H. F., Anderson, D., Kuh, D., Sandin, S., Giles, G. G., Bruinsma, F., Hayashi, K., Lee, J. S., Mizunuma, H., Cade, J. E., Burley, V., Greenwood, D. C., Goodman, A., Simonsen, M. K., Adami, H. O., Demakakos, P., & Weiderpass, E. (2017). Early menarche, nulliparity and the risk for premature and early natural menopause. Human reproduction (Oxford, England), 32(3), 679–686. https://doi.org/10.1093/humrep/dew350 3.Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18(4):483-91. doi: 10.3109/13697137.2015.1020484. Epub 2015 Apr 7. PMID: 25845383; PMCID: PMC4581591. 4.Sullivan, S. D., Sarrel, P. M., & Nelson, L. M. (2016). Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertility and sterility, 106(7), 1588–1599. https://doi.org/10.1016/j.fertnstert.2016.09.046 5.Huang, Qy., Chen, Sr., Chen, Jm. et al. Therapeutic options for premature ovarian insufficiency: an updated review. Reprod Biol Endocrinol 20, 28 (2022). https://doi.org/10.1186/s12958-022-00892-8