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hypothalamic amenorrhea

Etiology: 1) functional hypothalamic amenorrhea - failure of LH surge required for ovulation - emotional stress - concurrent illness - sudden weight loss - increase in exercise 2) amenorrhea associated with anorexia - failure of LH surge required for ovulation - estrogen secretion is low 3) athlete's amenorrhea - similar to anorexia 4) infiltration of hypothalamus - lymphoma - sarcoidosis Epidemiology: - 3-5% of women aged 18-40 years Pathology: - abnormality in pulsatile secretion of GnRH a) complete absence of GnRH pulses b) nocturnal pattern reminiscent of prepubertal children c) low amplitude GnRH pulses History: - eating disorder Clinical manifestations: - amenorrhea lasting > 3 months or time between menses regularly exceeds 45 days Laboratory: 1) serum gonadotropins (FSH in serum & LH in serum) low to low normal - FSH in serum low to low normal - estradiol in serum low to low normal - may be in normal range for women in follicular phase of menstrual cycle 2) beta-chorionic gonadotropin in serum [3] 3) serum GnRH inappropiately low 4) progesterone challenge test is negative [1] 5) thyroid function similar to euthyroid sick syndrome - thyroid-stimulating hormone in serum low to low normal [3] - free thyroxine in serum low to low normal [3] 7) prolactin in serum elevated with prolactinoma or antipsychotic [3] 8) anti-Mullerian hormone in serum [3] 9) serum testosterone & serum DHEA sulfate elevated in patients with signs of hyperandrogenism [3] 10) 8 AM 17-hydroxyprogesterone in serum if late-onset congenital adrenal hyperplasia is a possibility [3] 11) if chronic illness suspected [3] - complete blood count - basic metabolic panel - liver function tests - erythrocyte sedimentation rate &/or C-reactive protein in serum 12) pregnancy test Radiology: - neuroimaging (MRI) if severe headaches, galactorrhea or laboratory evidence of pituitary disorder [3] - bone mineral density if amenorrhea exceeds 6 months [3] Management: 1) women NOT seeking fertility a) estrogen/progestin containing oral contraceptives - avoid long-term consequences of estrogen deficiency - avoid endometrial hyperplasia resulting from lack of progesterone b) do not prescribe hormonal contraceptives unless needed for contraception [3] 2) women seeking fertility - pulsatile GnRH therapy - clomiphene citrate - exogenous gonadotropin therapy 3) nutritional supplementation for women below 10th percentile of weight for height 4) address psychosocial issues [3]

General

amenorrhea (oligomenorrhea)

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16. American College of Physicians, Philadelphia 1998, 2012
  2. Gordon CM. Clinical practice. Functional hypothalamic amenorrhea. N Engl J Med. 2010 Jul 22;363(4):365-71 PMID: 20660404
  3. Gordon CM et al. Functional hypothalamic amenorrhea: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2017 Mar 22; PMID: 28368518