What is Menopause?

Menopause is the biological stage in a woman s life that occur when she stops having a period, The word menopause refers to the last menstrual bleed. Menopause is clinically defined as amenorrhoea of 12 months duration after the final menstrual period. Menopause does not usually occur until a woman has reached her late forties or early fifties. In the United Kingdom the average age of menopause is 51.4 years. Periods may become less frequent or lighter over months or years before the stop. Symptoms of menopause include: hot flushes, night sweats, sleep disturbance, depression and mood disturbance, memory and attention deficits, vaginal dryness, frequent urinary tract,and Joint pain. For most women,the symptoms spontaneously resolve within a few years (1-2 years). However, about one third of postmenopausal women will experience symptoms for longer periods and in about 10% women the symptoms are severe enough to warrant medical help.There are certain long-term health issues. Resulting from estrogen deficiency, these health issues primarily consist of an increased risk of cardiovascular disease and osteoporosis, which increases the risk of bone fractures.

What is Premature Ovarian Failure (Premature menopause)?

The term premature menopause (premature ovarian failure) is defined as the occurrence of menopause before the age 40. . Premature ovarian failure can present at varying ages and in many forms. If premature menopause happens before puberty, the woman will present with lack of sexual developments and her periods will not start. However, if the condition presents after puberty, the woman will suffer from amenorrhoea and infertility. The diagnosis of premature menopause can be a shattering experience to the women and her family. Many women feel robbed .

Since the woman's estrogen production is low, hormone replacement treatment is prescribed until. the average age of menopause to put the brakes on the premature ageing effects of menopause such as hot flushes, night sweats, vaginal dryness, low mood and depression and osteoporosis.In contrast with hormone replacement usage after the average age of menopause , the risk of breast cancer is not higher than that in the general population. Also, the risk of blood clot assocaited with hormone replacement is lower in this age group. Modification of general life style is recommended including maintaining a healthy weight, avoid smoking, minimising alcohol cionsumption, regular excercise etc. Non hormone treatment is not recommended as an alternative to hormone replacement unless there are contraindication to the use of oestrogen such as cancer breast.  

Incidence of premature menopause

About 1-4% of women will experience menopause before the age 40 years and 5% before the age of 45 years. The incidence of premature ovarian failure or the early menopause is on the increase (Arora and Polson, 2011). Premature ovarian failure accounts for about 10% of amenorrhoea and 1% of all cases of infertility.

Early ovarian aging

Early ovarian aging affect about 10% of women. It refers to a condition of low ovarian reserve at a young age and accelerated loss of ovarian follicles. Most women with early ovarian aging have no symptoms and have regular menses. However, continuning accelerated follicular depletion will eventually result in loss of fertility and menstrual irregularities and finally early menopause.

Diagnosis of premature menopause?

The diagnosis is based on clinical presentation and blood tests. FSH more than 25 iu and low estrogen level . A confirmatory second FSH measurement should be taken after 6 weeks from the first test as ovarian functions can fluctuate and a single normal FSH does not exclude the diagnosis. AMH level is low in women with premature ovarian failure but is not specific and is not considered diagnostic.

What are the causes of premature menopause?

In the majority of cases no medical cause can be found. However, tobacco use, nulliparity, and family history are associated with earlier menopause. Some of the known causes include:

• Congenital, if the ovaries failed to develop and are absent from birth.
• Chromosomal abnormalities, such as Turner's syndrome, where the ovaries contain only a few follicles.
• Genetic (Fragile X premutation). Some women's ovaries run out of eggs long before their middle age. This is possibly due to an increased rate of disappearance of follicles. The incidence of familial premature ovarian failure (POF) varies from 4% to 30%. The risk of a female relative developing POF may be as high as 100% in familial POF and as low as 1% in sporadic cases.  
• Autoimmune disease. Thyroid disease, type 1 diabetes, and Addison disease are common in women with premature ovarian failure. Ovarian antibodies act against the ovaries.
• The ovaries are physically damaged by infections, such as the mumps, or by cancer treatments, such as pelvic radiotherapy or chemotherapy. This later group is increasing in number because of the longer survival of cancer patients due to advances in both diagnostic modalities and treatment available.
• Metabolic syndromes such as Galactosemis
• The ovaries were surgically removed because of cancer or other causes.

What fertility options are available for women with PMM?

• At present, the only realistic chance of a pregnancy for women with premature menopause lies through egg donation.
• Many fertility centers are now offering ovarian tissue freezing and storage for women with a positive family history of premature menopause. The aim is restoration of ovarian function through the transplantation of ovarian tissue. Although the technique of transplantation remains experimental, successful transplantations has been reported. Bedaiwy and colleagues (2008) reported that ovarian function was restored within 120 days. Furthermore, they reported six pregnancies. Anderson and colleagues (2008) described freezing of a whole ovary from six women (age 26-35 years) prior to cancer treatment.  After a storage period of between 17 and 32 months, ovarian transplantation was performed. In all cases, the transplanted tissue restored menstrual cycles within 20 weeks of the transplantation. Four of the six women conceived following assisted reproduction: two of the women delivered a single healthy child one woman miscarried.
• Egg freezing and storage is another option for women with a positive family history of premature menopause and has no partner. Many IVF centers are currently offering egg freezing. Technological improvements in egg vitrification offer young healthy women the possibility of preserving eggs until the less fertile years of life. The best age for egg vitrification is probably under 30 years. However, unrealistic reliance on the store of vitrified eggs may lead some women to defer pregnancy for many years only to experience disappointment when the stored eggs later fail to fertilise or implant.
• IVF with donated eggs and nuclear transfer is another possible future treatment. Here the nucleus of a healthy donor egg is replaced with the nucleus taken from a skin cell that 'would be a mother'. The donor egg is then fertilised by the male partner’s sperm and the resulting embryo is subsequently transferred into the recipient.
• Embryo donation is another option if the male partner is also infertile.
  
• A stem cell treatment has been recently used to reverse the early menopause in several women. The women had transplanted cells from their bone marrow raising the prospect of restoring fertility and eliminating the need for hormone replacement therapy.