amenorrhea (oligomenorrhea)

Introduction

Absence of menstruation in a woman of reproductive age.

Classification

• primary amenorrhea occurs when an adolescent female reaches 15 years of age without reaching menarche (i.e. no menses)
• secondary amenorrhea occurs when there is an absence of menses for 3-6 months in a previously normal menstruating woman
  • in a woman who discontinues oral contraceptives, amenorrhea can last up to 3 months; longer duration should be investigated
• oligomenorrhea is < 6 menses/year

Etiology

• pregnancy (most common cause of secondary amenorrhea)
• menopause
• hypothalamic amenorrhea
  • functional hypothalamic amenorrhea
    • failure of LH surge required for ovulation
    • emotional stress
    • concurrent illness
    • sudden weight loss
    • increase in exercise
  • amenorrhea associated with anorexia
    • failure of LH surge required for ovulation
    • estrogen secretion is low
  • athlete's amenorrhea - similar to anorexia
• hyperprolactinemia (20%)
  • prolactin inhibits release of GnRH from hypothalamus
  • diminished FSH & LH secretion from pituitary
• Sheehan's syndrome
• polycystic ovary disease
• Asherman's syndrome
• structural abnormalities associated with primary amenorrhea (15% of primary amenorrhea)
  • imperforate hymen
  • absence of cervix or uterus
  • absence of vagina (vaginal aplasia)
• chromosomal aberrations (50% of primary amenorrhea)
  • Turner's syndrome
  • mosaicism
• endocrine disorders
  • uncontrolled diabetes mellitus
  • insulin resistance, acanthosis nigricans
  • hyperthyroidism & hypothyroidism
  • Cushing's syndrome
  • adrenogenital syndrome
• pharmaceuticals
  • antipsychotics, metoclopramide
• premature ovarian failure

History

• last menstrual period, sexual activity, possibility of pregnancy, menstrual pattern, dietary or exercise changes, history of dilatation & curettage, post-partum infection or hemorrhage, weight changes, headaches, head injury, hot flashes, night sweats, dyspareunia, galactorrhea

Clinical manifestations

• 1/3 of women with hyperprolactinemia will have galactorrhea
• symptoms of thyroid or adrenal disease may be present
• pelvic exam may be abnormal
  • ovarian or adnexal mass
• visual field disturbances may be present with pituitary tumor
• breast development & other secondary sexual characteristics may be abnormal
• hyperandrogenism & virilization may be present
  • hirsutism, clitoromegaly, acne
• evidence of anorexia may be present
• evidence of stress or excessive exercise

Laboratory

• pregnancy test in all sexually-active women
• serum FSH, serum LH
  • low or normal in
    • hypothalamic amenorrhea
    • pituitary adenoma
    • Sheehan's syndrome
    • adrenogenital syndrome
  • normal in
    • Asherman's syndrome
    • polycystic ovary syndrome (serum LH may be increased)
  • elevated in ovarian failure
    • Turner's syndrome
    • premature ovarian failure
    • elevated serum FSH x 2 = primary ovarian failure
    • chemotherapy or pelvic irratiation
  • increased or normal in primary amenorrhea
• serum estradiol
  • low in
    • hypothalamic amenorrhea (hypothalamic hypogonadism)
      • stress weight loss, exercise
    • pituitary adenoma, hyperprolactinemia
    • Sheehan's syndrome
• Turner's syndrome
• premature ovarian failure
• hypothyroidism
  • normal in:
    • Asherman's syndrome
    • polycystic ovary syndrome
  • increased or normal in: adrenogenital syndrome
• serum prolactin:
  • elevated with prolactinoma
  • serum FSH & serum LH low with prolactinoma
  • unnecessary with normal-high serum FSH & serum LH
• thyroid function tests
  • first test if primary ovarian insufficiency confirmed
  • serum TSH
    • may (or may not) be unnecessary with normal-high serum FSH & serum LH & no signs of hyperthyroidism
    • free T4
• serum glucose
• chromosomal evaluation (karyotyping)
  • patients under 30 years of age with ovarian failure
  • suspected genetic disorder, Turner's syndrome
• progesterone challenge test*
  • evaluation of secondary amenorrhea
  • assesses estrogen status & outflow tract competency
  • no bleeding occurs with
    • hypothalamic hypogonadism
    • anorexic amenorrhea or athlete's amenorrhea
    • estrogen deficiency
    • outflow tract obstruction
  • bleeding suggests normal estrogen state & suggest possible hyperandrogenism (polycystic ovary syndrome)
  • medroxyprogesterone is given for 5-10 days
    • a normal response is withdrawal bleeding within 10 days
  • not indicated if serum estradiol is low
• estrogen/progestin cycle test
  • indicated by progesterone challenge test
  • progesterone challenge test is repeated after 21 days of conjugated estrogens
  • absence of bleeding suggests an outflow tract abnormality
    • Asherman's syndrome
• see ARUP consult

* after negative pelvic ultrasound if history of pelvic procedure

Diagnostic procedures

• pelvic ultrasound* if history of dilatation & curretage or other pelvic procedure (rule out Asherman's syndrome)

* transvaginal ultrasound

Radiology

• computed tomography (CT) or magnetic resonance imaging (MRI) to rule out pituitary tumor

Complications

• low bone mineral density, risk of fracture

Management

• anovulatory amenorrhea, including primary amenorrhea
  • oral contraceptives containing estrogen
    • premenopausal women with oligomenorrhea/amenorrhea +
      • decreased serum estradiol
  • 10 mg medroxyprogesterone acetate for 10 days every other month to prevent endometrial hyperplasia
  • normal menstrual cycle is regained with weight gain in women with anorexic amenorrhea
  • patient education
    • treatment for induction of ovulation is available
    • fertility is achievable
    • use of progestational agent alone does not provide contraceptive protection
• see hyperprolactinemia
• hypoestrogenemic amenorrhea
  • oral contraceptives for younger patients
  • conjugated estrogens (Premarin) 0.625 mg days 1-25
    • add medroxyprogesterone acetate (Provera) 10 mg on days 16-25
  • replenishment of fat stores if indicated
  • adequate calcium intake to reduce risk of osteoporosis
• hypothalamic amenorrhea: -reduce exercise, improve nutrition, emotional support 2]

More general terms

• sign/symptom
• menstrual disorder

More specific terms

• hypothalamic amenorrhea
• premature ovarian failure (premenopausal anovulation)

Additional terms

• dysmenorrhea (menstrual pain)