lactotrophs 120 min- FSH 60 min- LH Hypothalamus GnRH pituitary Estradiol +/- Progesterone _ FSH L H Ovary Uterus Ovulation Antral follicle >2mm

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1 lactotrophs Hypothalamus GnRH 120 min- 60 min- LH Progesterone _ pituitary L H + Ovary + Estradiol +/- Uterus Antral follicle >2mm Ovulation Preovulatory follicles atresia Follicular phase Luteal phase Cycle Days estrogen LH 1

2 follicular luteal Stabilizes the lining (1) PROLIFERATIVE PHASE Concurrent with follicular maturation and stimulated by estrogens (2) SECRETORY PHASE Concurrent with luteal phase and influenced by progesterone (3) MENSTRUAL PHASE Begins as hormone production by corpus luteum declines 2

3 Amerrhea or Oligomerrhea Neurologic symptoms (i.e. headaches, visual changes) hypothalamic- Pituitary lesions Signs of hyperandrogenism (hirsutism, acne) MRI Rapid onset Virlization Progressive symptoms Labs rmal adrenal or ovarian tumor Possible Late-onset CAH *Cushings etiology Testosterone >40mIU/mL :LH >1 DHEAS OVARIAN FAILURE Estradiol<50pg/ml FT4 FT4 Pelvic ultrasound History (medication, uterine factor CT scan of abdomen FUNCTIONAL HYPOTHYROID HYPERTHYROID Breast stimulation, HYPOTHALAMIC stress) AMENORRHEA MRI of pituitary Lipid profile etiology Treatment *Creatinine Pelvic exam *Transvaginal *oral glucose (Chapt.7) *AST *Hormone ultrasound tolerance test History (iatrogenic) withdraw *testosterone *endometrial biopsy *karyotype etiology of stress Levothyroxine *17-OH progesterone APS *r/o organic cause *lipid profile *24 hour cortisol Screen for thyroid HYPERPROLACTINEMIA Microprolactima Macroprolactima *fragile X testing ASHERMANS al contraceptives Dopamine agonist Dopamine agonist *spirolactone *lifestyle changes HRT Stress management oral contraceptives surgery *Support group HRT/BCP UNEXPLAINED/ HYPOTHALAMIC DYSFUNCTION 3

4 Headaches Blurry vision Diabetes insipidus Breast discharge Constipation Diahhrea Hot flashes Insomnia Sexual dysfunction Excess hair growth Acne Change in weight 4

5 Amerrhea or Oligomerrhea Neurologic symptoms (i.e. headaches, visual changes) hypothalamic- Pituitary lesions Signs of hyperandrogenism (hirsutism, acne) MRI Rapid onset Virlization Progressive symptoms Labs rmal adrenal or ovarian tumor Possible Late-onset CAH *Cushings etiology Testosterone >40mIU/mL :LH >1 DHEAS OVARIAN FAILURE Estradiol<50pg/ml FT4 FT4 Pelvic ultrasound History (medication, uterine factor CT scan of abdomen FUNCTIONAL HYPOTHYROID HYPERTHYROID Breast stimulation, HYPOTHALAMIC stress) AMENORRHEA MRI of pituitary Lipid profile etiology Treatment *Creatinine Pelvic exam *Transvaginal *oral glucose (Chapt.7) *AST *Hormone ultrasound tolerance test History (iatrogenic) withdraw *testosterone *endometrial biopsy *karyotype etiology of stress Levothyroxine *17-OH progesterone APS *r/o organic cause *lipid profile *24 hour cortisol Screen for thyroid HYPERPROLACTINEMIA Microprolactima Macroprolactima *fragile X testing ASHERMANS al contraceptives Dopamine agonist Dopamine agonist *spirolactone *lifestyle changes HRT Stress management oral contraceptives surgery *Support group HRT/BCP UNEXPLAINED/ HYPOTHALAMIC DYSFUNCTION Amerrhea or Oligomerrhea Neurologic symptoms (i.e. headaches, visual changes) hypothalamic- Pituitary lesions MRI 5

6 Amerrhea or Oligomerrhea Signs of hyperandrogenism (hirsutism, acne) Rapid onset Virlization Progressive symptoms Labs rmal adrenal or ovarian tumor Possible Late-onset CAH *Cushings etiology Testosterone >40mIU/mL :LH >1 DHEAS OVARIAN FAILURE Estradiol<50pg/ml FT4 FT4 Pelvic ultrasound History (medication, uterine factor CT scan of abdomen FUNCTIONAL HYPOTHYROID HYPERTHYROID Breast stimulation, HYPOTHALAMIC stress) AMENORRHEA MRI of pituitary Lipid profile etiology Treatment *Creatinine Pelvic exam *Transvaginal *oral glucose (Chapt.7) *AST *Hormone ultrasound tolerance test History (iatrogenic) withdraw *testosterone *endometrial biopsy *karyotype etiology of stress Levothyroxine *17-OH progesterone APS *r/o organic cause *lipid profile *24 hour cortisol Screen for thyroid HYPERPROLACTINEMIA Microprolactima Macroprolactima *fragile X testing ASHERMANS al contraceptives Dopamine agonist Dopamine agonist *spirolactone *lifestyle changes HRT Stress management oral contraceptives surgery *Support group HRT/BCP UNEXPLAINED/ HYPOTHALAMIC DYSFUNCTION Amerrhea or Oligomerrhea >40mIU/mL :LH >1 OVARIAN FAILURE Estradiol<50pg/ml FUNCTIONAL HYPOTHALAMIC AMENORRHEA etiology (iatrogenic) *karyotype APS Screen for thyroid *fragile X testing etiology of stress r/o organic cause HRT *Support group Stress management HRT/BCP Amerrhea or Oligomerrhea >40mIU/mL :LH >1 OVARIAN FAILURE Estradiol<50pg/ml FUNCTIONAL HYPOTHALAMIC AMENORRHEA etiology iatrogenic *karyotype APS Screen for thyroid *fragile X testing etiology of stress r/o organic cause HRT *Support group Stress management HRT/BCP 6

7 Hansen, 2008 iatrogenic *karyotype APS Screen for thyroid fragile X testing 7

8 iatrogenic *karyotype APS Screen for thyroid fragile X testing Thyroid Stimulating Hormone () Antithyroid peroxidase antibodies Antithyroglobulin antibodies *Bakalov V.K., 2002 Laureti,

9 iatrogenic *karyotype APS Screen for thyroid fragile X testing Marozzi, 2000;Uzielle,1999 Kogan, 2008 *Lancet, 1997;350,pg 1047 **Jacobsen,1997, Beiser AS,2009 **Lokkegaard,

10 Amerrhea or Oligomerrhea >40mIU/mL :LH >1 OVARIAN FAILURE Estradiol<50pg/ml FUNCTIONAL HYPOTHALAMIC AMENORRHEA etiology History (iatrogenic) *karyotype APS Screen for thyroid *fragile X testing etiology of stress r/o organic cause HRT *Support group Stress management HRT/BCP 10

11 stress Neuromodulation GABA, NE, 5-HT Hypothalamic adjustment NPY, CRH, TRH, GnRH Pituitary Glands Thyroid, ovary Adrenal, adipocytes Adapted Yen and, jaffe 2004 *Berga SL, 2005 Amerrhea or Oligomerrhea FT4 FT4 HYPOTHYROID HYPERTHYROID Levothyroxine *lipid profile Treatment 11

12 Amerrhea or Oligomerrhea etiology History (medication, Breast stimulation, stress) MRI of pituitary *Creatinine *AST HYPERPROLACTINEMIA Microprolactima Macroprolactima Dopamine agonist oral contraceptives Dopamine agonist surgery Amerrhea or Oligomerrhea Labs rmal uterine factor Pelvic exam *hormone withdraw ASHERMANS 12

13 Amerrhea or Oligomerrhea Labs rmal uterine factor Pelvic exam *hormone withdraw *Transvaginal ultrasound *testosterone Lipid profile *oral glucose tolerance test *endometrial biopsy *17-OH progesterone ASHERMANS al contraceptives *spirolactone *lifestyle changes UNEXPLAINED/ HYPOTHALAMIC DYSFUNCTION Amerrhea or Oligomerrhea Signs of hyperandrogenism (hirsutism, acne) Rapid onset Virlization Progressive symptoms adrenal or ovarian tumor Testosterone DHEAS Pelvic ultrasound CT scan of abdomen Amerrhea or Oligomerrhea Signs of hyperandrogenism (hirsutism, acne) Rapid onset Virlization Progressive symptoms Possible Late-onset CAH Cushings *Transvaginal ultrasound *testosterone Lipid profile oral glucose tolerance test *endometrial biopsy *17-OH progesterone *24-urine cortisol al contraceptives *spirolactone *lifestyle changes 13

14 Criteria for polycystic ovary syndrome. Revised 2003 consensus on diagstic criteria and long-term health risks related to polycystic ovary syndrome Fertility and Sterility Volume 81, Issue 1, January 2004, Pages

15 Johnstone, submitted Johnstone, submitted Task force: Fertility and Sterility, Volume 91, issue 2 February 2009, Pages

16 Amerrhea or Oligomerrhea Neurologic symptoms (i.e. headaches, visual changes) hypothalamic- Pituitary lesions Signs of hyperandrogenism (hirsutism, acne) MRI Rapid onset Virlization Progressive symptoms Labs rmal adrenal or ovarian tumor Possible Late-onset CAH *Cushings etiology Testosterone >40mIU/mL :LH >1 DHEAS OVARIAN FAILURE Estradiol<50pg/ml FT4 FT4 Pelvic ultrasound History (medication, uterine factor CT scan of abdomen FUNCTIONAL HYPOTHYROID HYPERTHYROID Breast stimulation, HYPOTHALAMIC stress) AMENORRHEA MRI of pituitary Lipid profile etiology Treatment *Creatinine Pelvic exam *Transvaginal *oral glucose (Chapt.7) *AST *Hormone ultrasound tolerance test History (iatrogenic) withdraw *testosterone *endometrial biopsy *karyotype etiology of stress Levothyroxine *17-OH progesterone APS *r/o organic cause *lipid profile *24 urine cortisol Screen for thyroid HYPERPROLACTINEMIA Microprolactima Macroprolactima *fragile X testing ASHERMANS al contraceptives Dopamine agonist Dopamine agonist *spirolactone *lifestyle changes HRT Stress management oral contraceptives surgery *Support group HRT/BCP UNEXPLAINED/ HYPOTHALAMIC DYSFUNCTION 16

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