Premature menopause

Premature Ovarian Failure – Causes & Treatment

What is premature ovarian failure?

 When a woman’s ovaries stop working before age 40, she is said to have premature ovarian insufficiency (POI) or premature ovarian failure (POF) also, known as premature menopause. It is a common condition, affecting 1–2% of women younger than 40 years of age. It found among 0.1% of women, younger than 30 years of age. When this happens, a woman’s menstrual cycles become irregular and stop. Her ovaries stop making hormones such as oestrogen and progesterone. Moreover, she stops releasing eggs (ovulating) regularly or at all.

Some women develop POF when they are teenagers, even before they start to have menstrual periods. If that happens, the teen will never experience normal function of her ovaries. For other women experiencing POF, their ovaries may continue to intermittently release (ovulate) eggs.  These women  may continue to have menstrual cycles for months or years before their ovaries completely shut down. For this reason, the currently used term POI is preferred to the older terminology “premature ovarian failure (POF).

 Causes of Premature Menopause 

In human females, the process of ovarian follicular maturation, or maturation of eggs, is a highly organised and complex process. Maturation of Eggs is the progressive maturation of small primordial follicles that progress to become large ovulatory follicles. When follicles eventually mature, the oocytes (eggs) are released from the surface of the ovary. They are collected by the uterine tube, and  proceed to become fertilised.

The causes of POF remains unknown in most cases. A genetic cause of POF is identified in few patients, i.e. in 5-7% of the total cases, whereas causes remains most often undiscovered. Fragile X syndrome is one of the genetic causes of POF which can be transmitted in the family.

Predisposing Factors of Premature ovarian failure

Women receiving cyclophosphamide for either kidney diseases or rheumatoid arthritis are at risk of developing POF.

Malnutrition and cigarette smoking are perhaps the only consistent environmental features associated with an earlier menopause.

The first known significant cause is damage to the ovaries, such as that caused by iatrogenic agents like chemotherapy or radiotherapy or pelvic surgery may be associated with ovarian failure. Surgical menopause may be induced by removal of ovaries, but interestingly hysterectomy to remove the uterus is also associated with an earlier menopause.

Premature ovarian failure (POF) may be considered as an autoimmune endocrine disease. Autoantibodies and lymphocyte subset changes are associated with premature ovarian failure. This problem can run in family as well.

What POF women experience?

Women with POF experience menopausal symptoms, such as hot flushes, night sweats and vaginal dryness, In addition, there is increased risk of developing osteoporosis because of the lengthened time of exposure to reduced oestrogen similar to those going through a natural menopause.

For most women, it can be an unexpected and distressing diagnosis, with unpleasant symptoms, but made worse by the fact that it coincides with infertility.

Infertility In POF

Premature ovarian failure (POF) is a disorder associated with female infertility, and it affects approximately 1% of women under the age of 40 yr. It can be attributed to two major mechanisms: follicle dysfunction and follicle depletion .

Despite having amenorrhea and markedly elevated serum gonadotropin levels, some women with karyotypically normal can go to spontaneous premature ovarian failure. Nevertheless, they have ovarian follicles that function intermittently. Graafian follicles capable of responding to these high FSH levels are faced with high serum LH levels as well, which might prevent normal follicle function.

Premenopausal women may be at risk for the development of osteoporosis. However, bone loss in women with amenorrhea from other causes has not been assessed. Women with POF have diminished general and sexual well-being and are less satisfied with their sexual lives than other women

Treatment of premature menopause

Many women with premature ovarian failure (POF)would benefit from symptom relief by the use of exogenous steroids, to compensate for the loss of ovarian hormone estrogen and possibly progesterone and androgens. Menopausal symptoms, such as hot flushes, night sweats and vaginal dryness can be relieved by oestrogen replacement, such as sequential HRT or oral contraceptive pill.

Management Of Infertility In POF

Infertility is a significant issue for most women undergoing POF. A number of treatment regimens have been evaluated with the aim of restoring fertility. However, treatments with clomiphene, Gonadotrophins, GNRH agonists or immunosuppressants do not significantly improve the chance of conception and are not used.

The only reliable fertility treatment is the use of donor eggs. It is an assisted reproductive procedure that is widely practised in most countries. At present, in vitro maturation of immature follicles is possible. But in vitro growth and maturation from stored ovarian tissue is not reliably achievable in humans. For women with impending POF, there may not be any alternatives. Young women about to begin cancer treatment are encouraged to attempt a cycle of IVF if time permits. They can go for storing  embryo or eggs  for later use.

Ovarian Transplantation In POF

 Young women suffering from impending POF may store ovarian tissue. This gives the hope that at a later stage their tissue can be implanted. Storing the use of ovarian tissue can help restore fertility. In vitro growth and maturation of immature follicles of frozen ovarian tissue may restore fertility.

Lifestyle Changes In POF

Women suffering from oestrogen deficiency will need counselling. They should be recommended a number of measures to protect against osteoporosis. It includes increased physical exercise, eating a diet rich in calcium and vitamin D and avoiding risk factors such as smoking and high alcohol intake.

Women with POF are advised to undergo HRT until the normal age of menopause. They require addition of testosterone to HRT to improve sexual function and wellbeing.

Premature ovarian failure (POF), a major life-changing condition that affects a significant proportion of young women. It remains an enigma and the researcher’s minefield. Among women surviving  childhood cancers POF is commonly seen. This is due to improved iatrogenic interventions POF sufferers  inevitably increase.

Patient Counselling

When primary ovarian failure is diagnosed in the adolescent female, the patient and her family are often unprepared for such news.  Its implications for compromised fertility and the need for long-term hormonal therapy is frustrating. Adolescents may demonstrate myriad emotions ranging from apathy or denial to depression. These emotions may be different from those of their parents or guardians. Parents can provide valuable insights about their daughters’ future. Ability to appreciate the significance of the diagnosis  and help in managing the situation is of utmost importance.

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