Premature Ovarian Failure – Causes & Treatment

What is premature ovarian failure?

 When a woman’s ovaries stop working before age 40, she has premature ovarian insufficiency (POI). This is  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 occurs  among 0.1% of younger women less than 30 years of age. When this happens, a woman’s menstrual cycles become irregular and stop. Her ovaries stop making hormones such as estrogen 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, POI is preferred to the older terminology “premature ovarian failure (POF).

Reasons for premature ovarian failure

In human females, the process of ovarian follicular maturation, or maturation of eggs, is a  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) extrude from the surface of the ovary. They travel through the uterine tube, and  proceed for fertilization.

The causes of POF remains unknown in most cases. A genetic cause occurs in few patients, i.e. in 5-7% of the total cases. In other patients  causes are unknown. Fragile X syndrome is one of the genetic causes of POF which transmits 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 of earlier menopause.
• The first known significant cause is damage to the ovaries, such as that caused by chemotherapy or radiotherapy or pelvic surgery. Extensive pelvic surgery may lead to ovarian failure. Surgical menopause follows removal of ovaries. Similarly, hysterectomy to remove the uterus  also leads to an earlier menopause.
• Premature ovarian failure (POF), at times is an autoimmune endocrine disease. Autoantibodies and lymphocyte subset changes are common 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  risk of developing osteoporosis because of the lengthened time of exposure to low estrogen. It is similar to those going through a natural menopause.

For most women, it is an distressing diagnosis, with unpleasant symptoms. But, the worse part is it can lead to infertility.

Infertility In POF

Premature ovarian failure (POF) is a disorder causing female infertility.  It affects approximately 1% of women under the age of 40 yr. It happens due to either follicle dysfunction or 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 ovarian failure

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 estrogen 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 are available with the aim of restoring fertility. However, treatments with clomiphene, Gonadotrophins, GNRH agonists or immunosuppressants do not significantly improve the chance of conception.

The only reliable fertility treatment is the use of donor eggs. It is an assisted reproductive procedure that can help patients with POF.  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 can try  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 they can opt for ovarian transplantation.  Storing the  ovarian tissue can help restore fertility. Also in vitro growth and maturation of immature follicles of frozen ovarian tissue may restore fertility.

Lifestyle Changes In POF

Women suffering from estrogen deficiency will need counselling. They can take a number of measures to protect against osteoporosis. It includes regular physical exercise, eating a diet rich in calcium and vitamin D.  Moreover, avoiding risk factors such as smoking and high alcohol intake helps in such cases.

Women with POF should 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 use of radiotherapy and cancer chemotherapy.

Patient Counselling

Diagnosis of primary ovarian failure in the adolescent female is a shocking news for the patient and her family. They are often not ready to accept  such news.  Its implications for infertility 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.