Premature Menopause

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, is a common condition, affecting

1–2% of women younger than 40 years of age and 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 and 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 and make hormones; 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).

The causes of POF are largely unknown

In human females, the process of ovarian follicular

maturation, or folliculogenesis, is a highly organised and

complex process. Folliculogenesis is the progressive

maturation of small primordial follicles that progress to

become large ovulatory follicles. When follicles eventually mature, the oocytes are released from the surface of the ovary, collected by the

uterine tube, and either proceed to become fertilised.

Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. 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 aetiology remains most often undiscovered. Fragile X syndrome is one of the genetic causes of POF which can be transmitted in the family.

 Women receiving cyclophosphamide for either progressive glomerulonephritis 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 pelvic surgery may be

associated with ovarian failure. Surgical menopause

may be induced by oophorectomy, 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 mostwomen, it can be an unexpected and distressing

diagnosis, with unpleasant symptoms, but made worse

by the fact that it coincides with infertility

Premature ovarian failure (POF) is a disorder associated with female infertility, and it affects approximately 1% of women under the age of 40 yr  and encompasses a heterogeneous spectrum of conditions . 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 spontaneous premature ovarian failure, nevertheless, 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.

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 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

Many women with 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.

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,

which 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, as storing an embryo is more likely to be successful than using a frozen follicle for later use.

In addition, young women may store ovarian tissue, in the hope that at a later stage their tissue can be reimplanted, or that the use of in vitro growth and maturation of immature follicles may restore fertility

Women suffering from oestrogen deficiency should be recommended a

number of measures to protect against osteoporosis, including 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 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, remains an enigma and the researcher's minefield. As women increasingly survive childhood cancers due to improved iatrogenic interventions, the number of POF sufferers will inevitably increase.