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Premature ovarian failure (POF) is a condition in which ovarian function is irreversibly lost in women under the age of 40. This condition occurs in at least 1% of all women and is a serious obstacle to the possibility of conception, negatively affecting women’s health.
How to suspect the development of premature ovarian failure?
The menstrual cycle will help to suspect the possibility of developing premature ovarian failure.
Namely:
- primary amenorrhea (there was not a single episode of menstruation during the woman’s life)
- or secondary amenorrhea (menstruation was earlier, but stopped).
With secondary amenorrhea, both a sudden cessation of menstruation and a change in the nature of the menstrual cycle are possible (short intervals between menstruation, with possible delays, scanty menstruation, up to complete suspension. There are also cases when, in this condition, menstruation does not resume after childbirth or taking combined oral contraceptives (CОС).
Also, women may complain of infertility, hot flashes, decreased libido, changes in skin condition – rapid signs of aging, dryness.
Is the absence of menstruation enough for us to confirm the diagnosis of premature ovarian failure?
It is worth noting that the symptoms of premature ovarian failure can be varied due to the periodic production of sex hormones by the ovaries or the conversion of androgens into estrogens – however, a low ovarian reserve will remain unchanged. Most of the international recommendations today advise to determine the level of FSH to confirm premature ovarian failure (follicle-stimulating hormone) on day 2-4 of the menstrual cycle twice with an interval of 4-6 weeks.
An indicator of more than 12-25 mIU/ml indicates ovarian failure. A very important indicator of ovarian reserve is the level of AMH (anti-Mullerian hormone). It is important that this indicator is higher than 1.1 ng/ml in women younger than 40 years.
In addition, it is worth investigating the level of: estradiol, prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (free T4).
Causes of premature ovarian failure
While in many cases the cause is unknown, the family history is clearly followed (when the early onset of menopause was observed in the mother, grandmother). In various studies, the prevalence of familial premature ovarian failure ranges from 4 to 31%.
It has been established that the causes of premature ovarian failure are multifactoriality, but the main ones remain:
- Genetic reasons
- Chromosomal (violation of the number of chromosomes, structural chromosomal rearrangements)
- Autoimmune diseases (most often AIT – autoimmune thyroiditis, rheumatoid arthritis)
- Iatrogenic (influence of certain drugs – cytostatics, chemotherapy), transferred radiation therapy
- Transferred surgical interventions on the ovaries
- Endometriosis, ovarian dermoid cysts.
Genetic factors
More than 50 genes involved in the development of premature ovarian insufficiency have been identified (Qin Y, Jiao X, Simpson JL, Genetics of primary ovarian insufficiency: new developments and opportunities. Нum Reprod Update (2015) 21:787–808.). Most of these genes are involved in folliculogenesis (the maturation process of follicles), ovarian steroidogenesis (production of sex hormones) and, depending on which genes or combinations of genes are involved, we can evaluate the course of premature ovarian failure.Premature ovarian failure can also be associated with X-linked chromosomal abnormalities, such as Turner syndrome and fragile X chromosome.
Autoimmune factors
The frequency of autoimmune diseases in women with premature ovarian failure is higher compared to women from the general population (La Marca A, Brozzetti A, Sighinolfi G, Marzotti S, Primary ovarian insufficiency: autoimmune causes. Curr Opin Obstet Gynecol (2010).The most common autoimmune disorders associated with premature ovarian failure are hypothyroidism and hyperparathyroidism. Less commonly associated with type 1 diabetes, celiac disease, myasthenia gravis, rheumatoid arthritis, alopecia, multiple sclerosis.
Iatrogenic effect.
More and more often, we work with women who have undergone oncology and during the treatment of which chemotherapy or radiation therapy was used. The effect depends on the type of therapy, applied dose, age at the time of treatment and ovarian reserve.Also, any surgical interventions on the ovaries can contribute to the development of premature ovarian failure.
What impact does premature ovarian failure have on a woman’s health and life?
The main symptoms that develop with a premature decrease in the ovarian reserve are caused by: hypoestrogenia, hypoprogesteronemia and hypoandrogenia.
Typical early symptoms are: hot flushes, increased sweating, rapid tendency to gain weight, anxiety, mood swings, depression, sleep disturbances, decreased libido, dry mucous membranes, loss of concentration, decreased memory retention.
Late complications of untreated PAD are: cardiovascular diseases, increased blood cholesterol, insulin resistance (excess production of insulin, which can provoke the development of type II diabetes), osteoporosis, depression, Alzheimer’s disease, Parkinson’s disease – complications that significantly affect quality of life of a woman.
Coronary heart disease was found to have a 48% higher risk in women with premature ovarian failure compared to women whose menstrual cycle ended around 50-51 years of age.
Bove et colleagues found a decline in cognitive function and an increase in Alzheimer’s disease in women who underwent surgery at a young age and, as a result, developed estrogen deficiency in the body.Hypoestrogenia in premature ovarian failure leads to resorption – loss of bone density (osteoporosis), as a result of susceptibility to fractures.
How and should the state of premature decrease of estrogen in the female body be corrected?
The latest scientific data, recommendations dedicated to the topic of premature ovarian failure point to the importance of maintaining a healthy lifestyle, balanced diet, physical activity, adequate sleep, and smoking cessation.
But the most important thing in the treatment and prevention of late complications of premature ovarian failure is the appointment of hormone replacement therapy (HRT), which must be selected individually, taking into account age, the cause of the hypoestrogen state, and concomitant diseases.
At the moment, there are effective means thanks to which a woman can fully live, work and enjoy life.