Premature Ovarian Insufficiency

Premature ovarian insufficiency is defined as menopause before the age of 40 years. It is the result of a decline in the normal activity of the ovaries at an early age. It presents with early onset of the typical symptoms of the menopause.

Premature ovarian insufficiency is characterised by hypergonadotropic hypogonadism. Under-activity of the gonads (hypogonadism) means there is a lack of negative feedback on the pituitary gland, resulting in an excess of the gonadotropins (hypergonadotropism). Hormonal analysis will show:

  • Raised LH and FSH levels (gonadotropins)
  • Low oestradiol levels

 

Causes

  • Idiopathic (the cause is unknown in more than 50% of cases)
  • Iatrogenic, due to interventions such as chemotherapy, radiotherapy or surgery (i.e. oophorectomy)
  • Autoimmune, possibly associated with coeliac disease, adrenal insufficiency, type 1 diabetes or thyroid disease
  • Genetic, with a positive family history or conditions such as Turner’s syndrome
  • Infections such as mumps, tuberculosis or cytomegalovirus

 

Presentation

Premature ovarian insufficiency presents with irregular menstrual periods, lack of menstrual periods (secondary amenorrhea) and symptoms of low oestrogen levels, such has hot flushes, night sweats and vaginal dryness.

 

Diagnosis

NICE guidelines on menopause (2015) say premature ovarian insufficiency can be diagnosed in women younger than 40 years with typical menopausal symptoms plus elevated FSH

The FSH level needs to be persistently raised (more than 25 IU/l) on two consecutive samples separated by more than four weeks to make a diagnosis. The results are difficult to interpret in women taking hormonal contraception.

 

Associations

Women with premature ovarian failure are at higher risk of multiple conditions relating to the lack of oestrogen, including:

  • Cardiovascular disease 
  • Stroke
  • Osteoporosis
  • Cognitive impairment 
  • Dementia
  • Parkinsonism

 

Management

Management involves hormone replacement therapy (HRT) until at least the age at which women typically go through menopause. HRT reduces the cardiovascular, osteoporosis, cognitive and psychological risks associated with premature menopause. It is worth noting there is still a small risk of pregnancy in women with premature ovarian failure, and contraception is still required.

There are two options for HRT in women with premature ovarian insufficiency:

  • Traditional hormone replacement therapy
  • Combined oral contraceptive pill

Traditional hormone replacement therapy is associated with a lower blood pressure compared with the combined oral contraceptive pill. The combined pill may be more socially acceptable (less stigma for younger women) and additionally acts as contraception.

Hormone replacement therapy before the age of 50 is not considered to increase the risk of breast cancer compared with the general population, as women would ordinarily produce the same hormones at this age. 

There may be an increased risk of venous thromboembolism with HRT in women under 50 years. The risk of VTE can be reduced by using transdermal methods (i.e. patches). 

 

Last updated June 2020
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