Aetiology
Causes of POF include:
genetic disorders
autoimmune disorders
infections
toxic causes (including chemotherapy or radiation)
galactosaemia
idiopathic.
Approximately 50% of cases remain unexplained. A family history of POF is a major risk factor for idiopathic POF, with the risk increased up to 6-fold in first-degree relatives of women with POF.[8]
Pathophysiology
The symptoms of POF are the result of hypo-oestrogenaemia secondary to cessation of ovarian function. All patients with POF will be found to have hypo-oestrogenaemia and elevated serum gonadotrophins, including both follicle-stimulating hormone (FSH) and luteinising hormone (LH).
Hypo-oestrogenaemia is usually the result of ovarian follicular depletion. Decreased ovarian secretion of estradiol, progesterone, and inhibin decreases negative feedback on the hypothalamus and pituitary, causing FSH and LH to rise. Uncommonly, POF can occur despite a normal number of remaining follicles as a result of antibodies to follicular receptors that render the ovary unreceptive to appropriate hormonal stimulation. Ovarian follicular depletion may be idiopathic (resistant ovary syndrome), or may be the result of exposure to toxic agents (e.g., chemotherapeutics or radiation), interference with blood supply to the ovary (e.g., during hysterectomy or uterine artery embolisation), or follicular destruction (e.g., autoimmune or mumps oophoritis). Some genetic syndromes (e.g., fragile X carriers or Turner syndrome) can result in a reduced number of follicles at the time of puberty or an abnormally rapid follicle turnover during the reproductive years.[9][10]
Classification
By age[1]
Normal menopause: after 45 years of age (average age 51)
Early menopause: between 40 and 45 years of age
Premature menopause: before 40 years of age
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