1 / 19

Hypothalamic Amenorrhea

Hypothalamic Amenorrhea. Feb 2, 2011 Grace Yeung. CLINICAL SCENARIO. 18 yo G0P0 woman referred to your clinic: “I haven’t had my period for 6 months” Menarche at age 12, normal 2° sex characteristics, no sexual activity

travis-ryan
Download Presentation

Hypothalamic Amenorrhea

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Hypothalamic Amenorrhea Feb 2, 2011 Grace Yeung

  2. CLINICAL SCENARIO • 18 yo G0P0 woman referred to your clinic: • “I haven’t had my period for 6 months” • Menarche at age 12, normal 2° sex characteristics, no sexual activity • Daily training for National Ballet School audition and has lost 5lbs (BMI 19) • Home-school, Mother is strict but supportive

  3. OBJECTIVES • How do you manage this patient? • What should you ask further on history? • What clinical findings should you look for? • What investigations do you order? • How do you diagnose etiology of amenorrhea? • Do you need to consult other services? • What are principles of long-term management?

  4. AMENORRHEA • The absence or abnormal cessation of menses • Transient, intermittent or permanent

  5. H-P-O AXIS & MENSTRUATION • Hypothalamus • Pituitary • Ovaries • Uterus and outflow tract

  6. HYPOGONADOTROPIC HYPOGONADISM • Functional Hypothalamic Amenorrhea • Anorexia or bulimia nervosa • Excessive exercise • Excessive weight loss or malnutrition • Hypothalamic or pituitary destruction • Central nervous system tumor • Constitutional delay of growth and puberty* • Chronic illness • Liver disease, Renal insufficiency, Diabetes, Immunodeficiency, Inflammatory bowel disease, Thyroid disease, Severe depression or psychosocial stressors • Cranial radiation • Congenital GnRH deficiency*, Kallmann syndrome* • Sheehan’s syndrome *causes of primary amenorrhea only

  7. HYPOTHALAMIC AMENORRHEA • Secondary amenorrhea due to suppression of H-P-O axis via GnRH pulsatility • No anatomic or organic disease = Diagnosis of Exclusion • STRESS • Energy deficit • Wt loss, eating disorder • Excessive exercise • Psychological • Genetic?

  8. PATHOPHYSIOLOGY • Genetic Basis for FHA (NEJM, Jan 20, 2011) • Genes associated with idiopathic hypogonadotropic hypogonadism (Congenital GnRH deficiency) in HA women • FGFR1, PROKR2, GNRHR, KAL1 • ? Susceptibility genes conferring functional deficiency in GnRH secretion in HA • Predisposition to HA • Triggered by hormonal, nutritional, or psychologic stressor • Selective advantage for survival in times of stress • Potential genetic screening tool in familial history

  9. Menstrual cycle Menarche, cycle frequency, duration of menses, LNMP, timing of amenorrhea Habits/Sports/Hobbies Wt loss, exercise, eating disorder Psychosocial Loss, family/work/school Meds Antipsychotics OCP GnRH agonists (Lupron), Depot medroxyprogesterone acetate (DMPA) PMH Chronic illness Prolactin Galactorrhea, H/A, visual field defect Thyroid Estrogen-deficiency Hot flashes, libido, vaginal dryness, poor sleep Obstetrical event/Instrumentation Hemorrhage, D&C, endometritis Sexual History Infertility FHx - Genetic HISTORY

  10. PHYSICAL EXAM • Ht, Wt, BMI • Tanner Staging • Thyroid exam • Visual Field • Galactorrhea • Hyperandrogenism • Virilization • Vomiting • Estrogen-deficiency

  11. INVESTIGATIONS • Rule out pregnancy – βhCG • Hypercortisol – Cortisol AM, ACTH • Hypothyroid – TSH, FT3, FT4 • Prolactinoma – Prl, MRI • Ovarian insufficiency – FSH, LH • Hyperandrogenism – Free testosterone, DHEAS • Chronic systemic illness – CBC, Ferritin, ACE, FBG, HbA1C, Karyotype, BMD, 25-OH Vit D, LFTs, albumin, lipid profile Estradiol, /low-normal LH and FSH

  12. INVESTIGATIONS

  13. INVESTIGATIONS • LH and FSH pulsatility study • Sampling q 10-15 min for 4-6 h • Gonadotropin profile • LH pulse type classification • GnRH test • LH and FSH pituitary response • Naloxone test • Opioidergic gonadtropic dysfunction • +ve if LH 2X baseline post-infusion • BUT, cannot rule-out if –ve as the amount of naloxone may not be enough to effectively counteract high opioidergic hypertone

  14. TREATMENT • Lifestyle modification (↓exercise and diet) • Opiod-R antagonist (Naltrexone cloridrate) • Acetyl-L-carnitine (ALC) • Leptin • Bone-density • Hormonal (low estrogen/OCP, androgens, IGF-1, leptin, bisphosphonates) vs.  Caloric intake to BMI and resumption of menses

  15. MANAGEMENT • Menstruation • Wt gain (? cut-off)/ ↓Exercise • Psychosocial • Stress reduction, CBT • Bone Density • Combined OCP, Ca 1200 mg/Vit D 1000 IU, baseline BMD • Infertility • Ovulation induction via pulsatile GnRH or exogenous gonadtropin • Poor response to clompiphene citrate

  16. CONSULTATION • Gynecology • Psychiatry • Pediatrician • Family Doctor • Sports Medicine • Dietician • Patient’s Family/Coach

  17. REFERENCES • Jean L Chan, Christos S Mantzoros, S.B. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhoea and anorexia nervosa.The Lancet, Volume 366, Issue 9479, 2 July 2005-8 July 2005, Pages 74-85 • The Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea.  Fertil Steril.  2004;82(suppl 1):S33 • Alessandro D. et al. Diagnostic and Therapeutic Approach to Hypothalamic Amenorrhea.Annals of the New York Academy of Sciences.10.1196/annals.1365.009 • James H. Liu Arthur H. Bill.Stress‐Associated or Functional Hypothalamic Amenorrhea in the Adolescent.Annals of the New York Academy of Sciences.10.1196/annals.1429.027 • Meczekalski B, Podfigurna-Stopa A, Warenik-Szymankiewicz A, Genazzani AR. Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations.Gynecol Endocrinol. 2008 Jan;24(1):4-11. • Vescovi JD, Jamal SA, De Souza MJ.Strategies to reverse bone loss in women with functional hypothalamic amenorrhea: a systematic review of the literature.Osteoporos Int. 2008 Apr;19(4):465-78. Epub 2008 Jan 8.

  18. THANK-YOU

More Related