Amenorrhea natural history, complications and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

If left untreated, patients with amenorrhea may progress to develop infertility and osteoporosis. Common complications of amenorrhea are based on underlying disorder that induce amenorrhea. Prognosis is generally excellent and the mortality rate of patients with amenorrhea is approximately less than 1%, generally in patients with brain lesions.

• If left untreated, all patients of amenorrhea may progress to develop infertility and osteoporosis.
• The majority of cases woth amenorrhea are result of four conditions, which include polycystic ovary syndrome, hypothalamic amenorrhea, hyperprolactinemia, and ovarian failure.
• Polycystic ovary syndrome (PCOS), if left untreated can lead to heart disease from elevated cholesterol and increased levels of androgens. Long periods of not having menstrual cycles leads to unopposed exposure of endometrium to estrogen, can result in endometrial cancer.^[1]
• In functional (hypothalamic) amenorrhea, the patient usually reports normal regular cycles in the past, with sudden interruption of menstrual cycles for more than 3 months. There is almost always a history of weight loss (severe), excessive exercise, or drastic emotional stress prior to cessation of menstruation.^[2]
• Premature ovarian failure presents with menopause before the age of 40 and elevated levels of gonadotropins. In the age group of 41 to 44 years, it is called pre-menopause. Patients of premature ovarian failure generally have a family history of ovarian failure.^[3]
• Amenorrhea from hyperprolactinemia can be caused by prolactin overproduction or dopamine suppression, and is mostly seen in middle aged women.^[4]

• Common complications of amenorrhea are based on the underlying disorder inducing amenorrhea. The majority of amenorrhea cases are caused by four conditions, which include polycystic ovary syndrome, hypothalamic amenorrhea, hyperprolactinemia, and ovarian failure.
• Common complications of amenorrhea from PCOS include:
  • Endometrial hyperplasia/Endometrial cancer
  • Insulin resistance/Diabetes mellitus type 2
  • High blood pressure
  • Dyslipidemia
  • Cardiovascular disease
  • Stroke
  • Miscarriage
  • Infertility
• Hyperprolactinemia leads to galactorrhea, decreased libido, and pregnancy complications. In cases with prolactinoma, massive enlargement of the tumor may affect vision and pituitary function. It may also cause osteopenia and osteoporosis in pre-menopausal women.^[5]
• Common complications of premature ovarian failure include infertility, osteoporosis, depression/anxiety, cardiac disease, and dementia.^[6]
• Patients with hypothalamic (functional) amenorrhea experience various complications, such as infertility, decrease in bone mineral density (BMD), increased risk for fracture, along with cardiovascular and psychological complicatons.^[2]
• The most important complication of premature ovarian failure is infertility, that is preventable to some extent with appropriate therapies. Bone loss and psychiatric disorders are other complications.^[7]

• Prognosis is generally excellent and the mortality rate of patients with amenorrhea is approximately less than 1%.
• Among patients of androgen insensitivity syndrome there is an increased risk of testicular cancer, and surveillance is needed appropriate intervals.
• Prognosis of polycystic ovary syndrome (PCOS) is generally good. Long term dietary management and exercise along with metformin therapy decreases the cardiovascular and pregnancy complications in the future.^[8]
• Prognosis is excellent for hyperprolactinemia due to microprolactinoma. Depending on the size of the tumor and the extent of tumor resection, the rate of recurrence may range from 20% to 50%. The majority of recurrent prolactinomas develop within the first 5 years.^[9]

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