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amenorrhea (oligomenorrhea)

Absence of menstruation in a woman of reproductive age. Classification: 1) primary amenorrhea occurs when an adolescent female reaches 15 years of age without reaching menarche (i.e. no menses) 2) 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 [5] 3) oligomenorrhea is < 6 menses/year Etiology: 1) pregnancy (most common cause of secondary amenorrhea) 2) menopause 3) hypothalamic amenorrhea a) functional hypothalamic amenorrhea 1] failure of LH surge required for ovulation 2] emotional stress 3] concurrent illness 4] sudden weight loss 5] increase in exercise b) amenorrhea associated with anorexia 1] failure of LH surge required for ovulation 2] estrogen secretion is low c) athlete's amenorrhea - similar to anorexia 4) hyperprolactinemia (20%) a) prolactin inhibits release of GnRH from hypothalamus b) diminished FSH & LH secretion from pituitary 5) Sheehan's syndrome 6) polycystic ovary disease 7) Asherman's syndrome 8) structural abnormalities associated with primary amenorrhea (15% of primary amenorrhea) a) imperforate hymen b) absence of cervix or uterus c) absence of vagina (vaginal aplasia) 9) chromosomal aberrations (50% of primary amenorrhea) a) Turner's syndrome b) mosaicism 10) endocrine disorders a) uncontrolled diabetes mellitus b) insulin resistance, acanthosis nigricans c) hyperthyroidism & hypothyroidism d) Cushing's syndrome e) adrenogenital syndrome 11) pharmaceuticals - antipsychotics, metoclopramide 12) 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) 1/3 of women with hyperprolactinemia will have galactorrhea 2) symptoms of thyroid or adrenal disease may be present 3) pelvic exam may be abnormal - ovarian or adnexal mass 4) visual field disturbances may be present with pituitary tumor 5) breast development & other secondary sexual characteristics may be abnormal 6) hyperandrogenism & virilization may be present - hirsutism, clitoromegaly, acne 7) evidence of anorexia may be present 8) evidence of stress or excessive exercise Laboratory: 1) pregnancy test in all sexually-active women 2) serum FSH, serum LH a) low or normal in 1] hypothalamic amenorrhea 2] pituitary adenoma 3] Sheehan's syndrome 4] adrenogenital syndrome b) normal in 1] Asherman's syndrome 2] polycystic ovary syndrome (serum LH may be increased) c) elevated in ovarian failure 1] Turner's syndrome 2] premature ovarian failure 3] elevated serum FSH x 2 = primary ovarian failure [2] 4] chemotherapy or pelvic irratiation d) increased or normal in primary amenorrhea 3) serum estradiol a) low in 1] hypothalamic amenorrhea (hypothalamic hypogonadism) - stress weight loss, exercise 2] pituitary adenoma, hyperprolactinemia 3] Sheehan's syndrome 4) Turner's syndrome 5) premature ovarian failure 6) hypothyroidism b) normal in: 1] Asherman's syndrome 2] polycystic ovary syndrome c) increased or normal in: adrenogenital syndrome 4) serum prolactin: - elevated with prolactinoma - serum FSH & serum LH low with prolactinoma - unnecessary with normal-high serum FSH & serum LH [2] 5) thyroid function tests - first test if primary ovarian insufficiency confirmed [5] - serum TSH - may (or may not) be unnecessary with normal-high serum FSH & serum LH & no signs of hyperthyroidism [2] - free T4 6) serum glucose 7) chromosomal evaluation (karyotyping) a) patients under 30 years of age with ovarian failure [2] b) suspected genetic disorder, Turner's syndrome 8) progesterone challenge test* a) evaluation of secondary amenorrhea b) assesses estrogen status & outflow tract competency c) no bleeding occurs with 1] hypothalamic hypogonadism 1] anorexic amenorrhea or athlete's amenorrhea 2] estrogen deficiency 3] outflow tract obstruction d) bleeding suggests normal estrogen state & suggest possible hyperandrogenism (polycystic ovary syndrome) e) medroxyprogesterone is given for 5-10 days - a normal response is withdrawal bleeding within 10 days f) not indicated if serum estradiol is low [5] 9) estrogen/progestin cycle test a) indicated by progesterone challenge test b) progesterone challenge test is repeated after 21 days of conjugated estrogens c) absence of bleeding suggests an outflow tract abnormality - Asherman's syndrome 10) see ARUP consult [3] * after negative pelvic ultrasound if history of pelvic procedure Special laboratory: - pelvic ultrasound* if history of dilatation & curretage or other pelvic procedure (rule out Asherman's syndrome) * transvaginal ultrasound [2] Radiology: - computed tomography (CT) or magnetic resonance imaging (MRI) to rule out pituitary tumor Complications: - low bone mineral density, risk of fracture Management: 1) anovulatory amenorrhea, including primary amenorrhea a) oral contraceptives containing estrogen - premenopausal women with oligomenorrhea/amenorrhea + - decreased serum estradiol b) 10 mg medroxyprogesterone acetate for 10 days every other month to prevent endometrial hyperplasia c) normal menstrual cycle is regained with weight gain in women with anorexic amenorrhea d) patient education - treatment for induction of ovulation is available - fertility is achievable - use of progestational agent alone does not provide contraceptive protection 2) see hyperprolactinemia 3) hypoestrogenemic amenorrhea a) oral contraceptives for younger patients b) conjugated estrogens (Premarin) 0.625 mg days 1-25 - add medroxyprogesterone acetate (Provera) 10 mg on days 16-25 c) replenishment of fat stores if indicated d) adequate calcium intake to reduce risk of osteoporosis 4) hypothalamic amenorrhea: -reduce exercise, improve nutrition, emotional support 2]

Related

dysmenorrhea (menstrual pain)

Specific

hypothalamic amenorrhea premature ovarian failure (premenopausal anovulation)

General

sign/symptom menstrual disorder

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 388-90
  2. Medical Knowledge Self Assessment Program (MKSAP) 11,14,16,17,18,19. American College of Physicians, Philadelphia 1998,2006,2012,2015,2018,2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. ARUP Consult: Amenorrhea The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/amenorrhea - Primary Amenorrhea Testing Algorithm https://arupconsult.com/algorithm/primary-amenorrhea-testing-algorithm - Secondary Amenorrhea Testing Algorithm https://arupconsult.com/algorithm/secondary-amenorrhea-testing-algorithm
  4. Klein DA, Poth MA. Amenorrhea: an approach to diagnosis and management. Am Fam Physician. 2013 Jun 1;87(11):781-8. Review. PMID: 23939500 Free Article
  5. NEJM Knowledge+ Endocrinology - Klein DA, Paradise SL, Reeder RM. Amenorrhea: A Systematic Approach to Diagnosis and Management. Am Fam Physician. 2019 Jul 1;100(1):39-48. PMID: 31259490 Free article. Review.