Premature Ovarian Failure (POF), also known as
primary ovarian insufficiency,
premature menopause, primary ovarian failure, hypergonadotropic hypogonadism, as well as
gonadal dysgenesis, is the loss of function of the ovaries before age 40. A commonly cited triad for the diagnosis is amenorrhea, hypergonadotropinism, and hypoestrogenism.
Incidence/prevalence
It has been estimated that POF affects 1% of the population. It affects approximately 1-4% of the female population in the U.S.
Presentation
Normally, ovaries supply women with eggs until about age 51, the average age of natural
menopauseMenopause is the time in a woman’s life when menstruation ends. It is part of a biological process that begins, for most women, in their mid-fifties. During this time, the ovaries gradually produce lower levels of natural sex hormones—estrogen and progesterone...
.
POF is not the same as a natural menopause, in that the dysfunction of the ovaries, loss of eggs, or removal of the ovaries at a young age is not a natural physiological occurrence.
Infertility is the result of this condition, and is the most discussed problem resulting from it, but there are additional health implications of the problem, and studies are ongoing. For example, osteoporosis or decreased bone density affects almost all women with POF due to an insufficiency of estrogen. There is also an increased risk of heart disease,
hypothyroidismHypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants.-Causes:...
in the form of
Hashimoto's thyroiditisHashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease where the body's own T-cells attack the cells of the thyroid. It was the first disease to be recognised as an autoimmune disease....
,
Addison's diseaseAddison's disease is a rare endocrine disorder in which the adrenal glands do not produce enough steroid hormones...
, and other auto-immune disorders.
Hormonally, POF is defined by abnormally low levels of
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
and high levels of
FSHFSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...
, which demonstrate that the ovaries are no longer responding to circulating FSH by producing estrogen and developing fertile eggs. The ovaries will likely appear shriveled.
Age of onset can be as early as the teenage years but varies widely. If a girl never begins menstruation, it is called primary ovarian failure. The age of 40 was chosen as the cut-off point for a diagnosis of POF. This age was chosen somewhat arbitrarily, as all women's ovaries decline in function over time, however an age needed to be chosen to distinguish usual menopause from the abnormal state of premature menopause. Premature ovarian failure however often has components to it that distinguish it from normal menopause.
By the age of 40, approximately one percent of women have POF. Women suffering from POF usually experience menopausal symptoms, which are generally more severe than the symptoms found in older menopausal women.
Causes
The cause of POF is usually
idiopathicIdiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind."...
. Some cases of POF are attributed to autoimmune disorders, others to genetic disorders such as
Turner syndromeTurner syndrome or Ullrich-Turner syndrome encompasses several conditions, of which monosomy X is most common. It is a chromosomal disorder in which all or part of one of the sex chromosomes is absent...
and
Fragile X syndromeFragile X syndrome, or Martin-Bell syndrome, is a genetic syndrome which results in a spectrum of characteristic physical, intellectual, emotional and behavioural features which range from severe to mild in manifestation....
. In many cases, the cause cannot be determined. Chemotherapy and radiation treatments for cancer can sometimes cause ovarian failure. In natural menopause, the ovaries usually continue to produce low levels of hormones, but in chemotherapy or radiation-induced POF, the ovaries will often cease all functioning and hormone levels will be similar to those of a woman whose ovaries have been removed. Women who have had their tubes tied, or who have had hysterectomies, tend to go through menopause several years earlier than average, likely due to decreased blood flow to the ovaries. Family history and ovarian or other pelvic surgery earlier in life are also implicated as risk factors for POF.
There are two basic kinds of premature ovarian failure. Case 1) where there are few to no remaining follicles and case 2) where there are an abundant number of follicles. In the first situation the causes include genetic disorders, autoimune damage, chemotherpy, radiation to the pelvic region, surgery, endometriosis and infection. In most cases the cause is unknown. In the second case one frequent cause is autoimmune ovarian disease which damages maturing follicles, but leaves the primordial follicles intact. Also, in some women FSH may bind to the FSH receptor site, but be inactive. By lowering the endogenous FSH levels with ethinyl estradiol (EE) or with a GnRH-a the receptor sites are freed and treatment with exogenous recombinant FSH activates the receptors and normal follicle growth and ovulation can occur.
The POF Fact Sheet lists potential causes of POF:
English: http://www.pofsupport.org/information/factsheet/fact_sheet_english.pdf
Laboratory
Serum
follicle-stimulating hormoneFollicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotropes of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH) measurement along can be used to diagnose the disease. Two FSH measurements with one-month interval have been a common practice. The anterior pituitary secretes FSH and LH at high levels due to the dysfunction of the ovaries and consequent low estrogen levels. Typical FSH in POF patients is over 40 mlU/ml (post-menopausal range).
Fertility
Between 5 and 10 percent of women with POF may spontaneously become pregnant. Currently no fertility treatment has been found to effectively increase fertility in women with POF, and the use of donor eggs with In-Vitro Fertilization (IVF) and adoption have become more popular as a means of becoming parents for women with POF. Some women with POF choose to live child-free. (See
Impaired Ovarian ReservePoor ovarian reserve is a condition of low fertility characterized by low numbers of remaining oocytes in the ovaries and usually accompanied by high FSH levels. Quality of the eggs may also be impaired as a 1989 study by Scott et al...
for a summary of possible treatment methods.)
Hormonal Replacement
It is important to initiate the hormonal replacement therapy after the diagnosis of POF, as untreated patients are at a great risk of bone loss due to increased osteoclast activities, resulting in osteopenia as well as osteoparosis. Furthermore, most of the patients develop symptoms of
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
deficiency, including vasomotor flushes and vaginal dryness, both of which respond to
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
therapy effectively. There are several contraindications of
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
supplement, including smokers over 35 years of age, uncontrolled
hypertensionHypertension is a chronic medical condition in which the blood pressure is elevated. It is also referred to as high blood pressure or shortened to HT, HTN or HPN. The word "hypertension", by itself, normally refers to systemic, arterial hypertension.Hypertension can be classified as either...
, uncontrolled
diabetes mellitusDiabetes mellitus —often referred to simply as diabetes—is a condition in which the body either does not produce enough, or does not properly respond to, insulin, a hormone produced in the pancreas. Insulin enables cells to absorb glucose in order to turn it into energy...
, or history of thromboemboli events. If the patient has strong family history of thromboemboli events, care must be taken to proceed with the hormonal replacement therapy. As the minimum, testing for
Factor V LeidenFactor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians...
,
Protein CProtein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme that is activated by thrombin into activated protein C . The activated form degrades Factor Va and Factor VIIIa...
, and
Protein SProtein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b...
should be performed to ensure the low risk of developing thromboemboli events while on the estrogen replacement.
The transdermal estradiol patch (typically 100 mcg) is commonly recommended because of several advantages. It provides the replacement by steady infusion rather than by bolus when taking daily pills. It also avoids the first-pass effect in the liver.
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