Amenorrhea Jean Amoura, MD, MSc
Amenorrhea <ul><li>Primary </li></ul><ul><ul><li>Absence of menses by age 16 with normal secondary sexual characteristics ...
Events of Puberty <ul><li>Thelarche (breast development) </li></ul><ul><ul><li>Requires estrogen </li></ul></ul><ul><li>Pu...
Are there secondary sexual characteristics?
Primary Amenorrhea <ul><li>Is there normal development of secondary sexual characteristcs? </li></ul><ul><li>NO </li></ul>...
Amenorrhea with  Immature  Secondary Characteristics FSH Serum level   Low / normal  High Hypogonadotropic hypogonadism  G...
Primary Amenorrhea <ul><li>Hypogonadism </li></ul><ul><ul><li>30% have genetic abnormality </li></ul></ul><ul><ul><ul><li>...
Primary Amenorrhea with  Immature  Sexual Characteristics <ul><li>Hypogonadism (gonadal failure) </li></ul><ul><ul><li>Gon...
Gonadal Dysgenesis <ul><li>Chromosomally abnormal </li></ul><ul><li>- Classic turner ’s syndrome (45XO) </li></ul><ul><li>...
Primary Amenorrhea with  Immature  Sexual Characteristics <ul><li>Hypogonadotropism </li></ul><ul><ul><li>Hypothalamic dys...
Are there secondary sexual characteristics?
Primary Amenorrhea <ul><li>Is there normal development of secondary sexual characteristics? </li></ul><ul><li>YES </li></u...
Primary Amenorrhea with Normal Secondary Characteristics <ul><li>Mullerian Anomalies </li></ul><ul><ul><li>Mullerian agene...
Mayer-Rokitansky-Kuster-Hauser Syndrome (utero-vaginal agenesis) <ul><li>15%  of  primary amenorrhea  </li></ul><ul><li>No...
Imperforate Hymen
Androgen Insensitivity <ul><li>Normal breasts but no sexual hair </li></ul><ul><li>Normal looking female external genitali...
Primary Amenorrhea <ul><li>Evaluation </li></ul><ul><ul><li>Pregnancy test </li></ul></ul><ul><ul><li>Physical exam to det...
Primary Amenorrhea <ul><li>Treatment </li></ul><ul><ul><li>Cyclic estrogen/progestin </li></ul></ul><ul><ul><li>Remove gon...
Secondary Amenorrhea <ul><li>Pregnancy! </li></ul><ul><li>CNS disorders </li></ul><ul><li>Pituitary gland </li></ul><ul><l...
Secondary Amenorrhea <ul><li>CNS disorders </li></ul><ul><ul><li>Chronic hypothalamic anovulation </li></ul></ul><ul><ul><...
Secondary Amenorrhea <ul><li>Pituitary disorders </li></ul><ul><ul><li>Hyperprolactinemia </li></ul></ul><ul><ul><ul><li>P...
Secondary Amenorrhea <ul><li>Ovulation disorders </li></ul><ul><ul><li>Polycystic ovarian syndrome </li></ul></ul><ul><ul>...
Asherman’s Syndrome
Secondary Amenorrhea <ul><li>History </li></ul><ul><ul><li>Nutrition/exercise habits, weight change </li></ul></ul><ul><ul...
Negative Pregnancy.test TSH ,PROLACTIN, Progesterone challenge test withdrawal bleeding   without withdrawal bleeding   hy...
Secondary Amenorrhea <ul><li>Treatment goals </li></ul><ul><ul><li>Discovery and treatment of underlying disorder </li></u...
Amenorrhea <ul><li>26 yo Gravida 0 with menarche at age 14 presents with one-year history of amenorrhea.  </li></ul>
Amenorrhea <ul><li>Sexually active, using condoms </li></ul><ul><li>No recent change in weight, skin, hair </li></ul><ul><...
Amenorrhea <ul><li>Exam  </li></ul><ul><ul><li>Overweight </li></ul></ul><ul><ul><li>No galactorrhea </li></ul></ul><ul><u...
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Amenorrhea

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  • There is a 5% lifetime incidence for some form of amenorrhea. Physiologic causes of amenorrhea are: Prepubertal status, pregnancy, lactation, and menopause
  • Irradiation risk at &gt;250 rads Kallmann’s = insufficient pulsatile GnRH
  • Constitutional delay: diagnosis of exclusion after negative workup including head CT/MRI. Bone age should be delayed as well.
  • With androgen insensitivity, there will typically be more breast development than pubic hair development.
  • M-K-K-H is second most common cause of primary amenorrhea (1/4000) Mullerian aplasia -&gt; nl breast devlpmt, body hair, blind vaginal pouch Check for renal abnormalities (present in 34%), skeletal abnormalities (12%)
  • Karyotype for patients with premature ovarian failure &lt;30yo If hirsutism is present, consider PCOS, congenital adrenal hyperplasia, Cushing’s, or ovarian tumors: check free testosterone
  • Purpose for inducing menses at least every 3 months is to prevent endometrial hyperplasia and cancer
  • Amenorrhea

    1. 1. Amenorrhea Jean Amoura, MD, MSc
    2. 2. Amenorrhea <ul><li>Primary </li></ul><ul><ul><li>Absence of menses by age 16 with normal secondary sexual characteristics </li></ul></ul><ul><ul><li>Absence of menses by age 14 without secondary sexual development </li></ul></ul><ul><li>Secondary </li></ul><ul><ul><li>Absence of menses for 6 months in a previously menstruating female </li></ul></ul>
    3. 3. Events of Puberty <ul><li>Thelarche (breast development) </li></ul><ul><ul><li>Requires estrogen </li></ul></ul><ul><li>Pubarche/adrenarche (pubic hair development) </li></ul><ul><ul><li>Requires androgens </li></ul></ul><ul><li>Menarche </li></ul><ul><ul><li>Requires: </li></ul></ul><ul><ul><li>GnRH from the hypothalamus </li></ul></ul><ul><ul><li>FSH and LH from the pituitary </li></ul></ul><ul><ul><li>Estrogen and progesterone from the ovaries </li></ul></ul><ul><ul><li>Normal outflow tract </li></ul></ul>
    4. 4. Are there secondary sexual characteristics?
    5. 5. Primary Amenorrhea <ul><li>Is there normal development of secondary sexual characteristcs? </li></ul><ul><li>NO </li></ul><ul><li>Think hypogonadism or hypogonadotropism </li></ul>
    6. 6. Amenorrhea with Immature Secondary Characteristics FSH Serum level Low / normal High Hypogonadotropic hypogonadism Gonadal dysgenesis
    7. 7. Primary Amenorrhea <ul><li>Hypogonadism </li></ul><ul><ul><li>30% have genetic abnormality </li></ul></ul><ul><ul><ul><li>Gonadal dysgenesis, Turner’s syndrome, mosaicism </li></ul></ul></ul><ul><li>Enzyme deficiencies </li></ul><ul><li>Kallmann’s syndrome, CNS tumors </li></ul><ul><li>Irradiation </li></ul><ul><li>Chemotherapy </li></ul><ul><li>Galactosemia </li></ul>
    8. 8. Primary Amenorrhea with Immature Sexual Characteristics <ul><li>Hypogonadism (gonadal failure) </li></ul><ul><ul><li>Gonadal dysgenesis </li></ul></ul><ul><ul><li>Irradiation </li></ul></ul><ul><ul><li>Chemotherapy </li></ul></ul><ul><ul><li>Galactosemia </li></ul></ul><ul><li>Note: gonadotropins (FSH/LH) will be high, similar to menopause </li></ul>
    9. 9. Gonadal Dysgenesis <ul><li>Chromosomally abnormal </li></ul><ul><li>- Classic turner ’s syndrome (45XO) </li></ul><ul><li>- Turner variants (45XO/46XX),(46X- abnormal X) </li></ul><ul><li>- Mixed gonadal dygenesis (45XO/46XY) </li></ul><ul><li>Chromosomally normal </li></ul><ul><li>- 46XX (Pure gonadal dysgeneis) </li></ul><ul><li>- 46XY (Swyer’s syndrome) </li></ul>
    10. 10. Primary Amenorrhea with Immature Sexual Characteristics <ul><li>Hypogonadotropism </li></ul><ul><ul><li>Hypothalamic dysfunction </li></ul></ul><ul><ul><ul><li>Kallmann syndrome </li></ul></ul></ul><ul><ul><ul><li>Anorexia nervosa </li></ul></ul></ul><ul><ul><ul><li>Space-occupying lesion of CNS </li></ul></ul></ul><ul><ul><ul><li>Marijuana use </li></ul></ul></ul><ul><ul><li>Pituitary damage (surgery/radiation) </li></ul></ul><ul><ul><li>Constitutional delay </li></ul></ul>
    11. 11. Are there secondary sexual characteristics?
    12. 12. Primary Amenorrhea <ul><li>Is there normal development of secondary sexual characteristics? </li></ul><ul><li>YES </li></ul><ul><li>Think </li></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Mullerian anomaly </li></ul></ul><ul><ul><li>Androgen insensitivity </li></ul></ul>
    13. 13. Primary Amenorrhea with Normal Secondary Characteristics <ul><li>Mullerian Anomalies </li></ul><ul><ul><li>Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) </li></ul></ul><ul><ul><li>Imperforate hymen </li></ul></ul><ul><ul><li>Transverse vaginal septum </li></ul></ul>
    14. 14. Mayer-Rokitansky-Kuster-Hauser Syndrome (utero-vaginal agenesis) <ul><li>15% of primary amenorrhea </li></ul><ul><li>Normal secondary development & external female genitalia </li></ul><ul><li>Normal female range testosterone level </li></ul><ul><li>Absent uterus and upper vagina & normal ovaries </li></ul><ul><li>Karyotype 46-XX </li></ul><ul><li>15-30% renal, skeletal and middle ear anomalies </li></ul>
    15. 15. Imperforate Hymen
    16. 16. Androgen Insensitivity <ul><li>Normal breasts but no sexual hair </li></ul><ul><li>Normal looking female external genitalia </li></ul><ul><li>Absent uterus and upper vagina </li></ul><ul><li>Karyotype 46, XY </li></ul><ul><li>Male range testosterone level </li></ul><ul><li>Treatment : gonadectomy after puberty + HRT </li></ul>
    17. 17. Primary Amenorrhea <ul><li>Evaluation </li></ul><ul><ul><li>Pregnancy test </li></ul></ul><ul><ul><li>Physical exam to determine presence of uterus </li></ul></ul><ul><ul><li>FSH </li></ul></ul><ul><ul><li>Karyotype </li></ul></ul>
    18. 18. Primary Amenorrhea <ul><li>Treatment </li></ul><ul><ul><li>Cyclic estrogen/progestin </li></ul></ul><ul><ul><li>Remove gonadal streaks if XY or mosaic </li></ul></ul><ul><ul><ul><li>Increased (52%) risk of gonadoblastomas, dysgerminomas, and yolk sac tumors </li></ul></ul></ul><ul><ul><li>Pulsatile GnRH for ovulation induction in select patients </li></ul></ul><ul><ul><li>Surgical resection of intrauterine, cervical, and vaginal adhesions/septa </li></ul></ul>
    19. 19. Secondary Amenorrhea <ul><li>Pregnancy! </li></ul><ul><li>CNS disorders </li></ul><ul><li>Pituitary gland </li></ul><ul><li>Thyroid </li></ul><ul><li>Ovary </li></ul><ul><li>Uterus </li></ul><ul><li>Systemic disorders </li></ul><ul><ul><li>Renal failure, liver disorders, DM </li></ul></ul><ul><li>Medications: anti-psychotics, reserpine </li></ul>
    20. 20. Secondary Amenorrhea <ul><li>CNS disorders </li></ul><ul><ul><li>Chronic hypothalamic anovulation </li></ul></ul><ul><ul><ul><li>Stress </li></ul></ul></ul><ul><ul><ul><li>Increased exercise levels </li></ul></ul></ul><ul><ul><ul><li>Anorexia nervosa </li></ul></ul></ul><ul><ul><li>Head trauma </li></ul></ul><ul><ul><li>Space-occupying lesions </li></ul></ul>
    21. 21. Secondary Amenorrhea <ul><li>Pituitary disorders </li></ul><ul><ul><li>Hyperprolactinemia </li></ul></ul><ul><ul><ul><li>Prolactinoma </li></ul></ul></ul><ul><ul><ul><li>Medications </li></ul></ul></ul><ul><ul><ul><li>PCOS </li></ul></ul></ul><ul><ul><ul><li>Renal failure </li></ul></ul></ul><ul><ul><li>Hypoprolactinemia </li></ul></ul><ul><ul><ul><li>Pituitary resection </li></ul></ul></ul><ul><ul><ul><li>Sheehan’s syndrome </li></ul></ul></ul><ul><li>Thyroid disorders </li></ul><ul><ul><li>Hyper- or hypothyroidism </li></ul></ul>
    22. 22. Secondary Amenorrhea <ul><li>Ovulation disorders </li></ul><ul><ul><li>Polycystic ovarian syndrome </li></ul></ul><ul><ul><li>Premature ovarian failure </li></ul></ul><ul><li>Uterine abnormalities </li></ul><ul><ul><li>Asherman’s syndrome </li></ul></ul><ul><ul><li>Cervical stenosis </li></ul></ul><ul><li>Drug-induced amenorrhea </li></ul><ul><ul><li>Hormonal contraceptives </li></ul></ul><ul><ul><li>GnRH analogues </li></ul></ul>
    23. 23. Asherman’s Syndrome
    24. 24. Secondary Amenorrhea <ul><li>History </li></ul><ul><ul><li>Nutrition/exercise habits, weight change </li></ul></ul><ul><ul><li>Sexual/contraceptive practice </li></ul></ul><ul><ul><li>History of uterine/cervical surgery </li></ul></ul><ul><li>Physical exam </li></ul><ul><ul><li>Height/weight </li></ul></ul><ul><ul><li>Hirsutism </li></ul></ul><ul><ul><li>Galactorrhea </li></ul></ul><ul><ul><li>Estrogen status of tissues </li></ul></ul><ul><li>Laboratory </li></ul><ul><ul><li>BhCG  PRL & TSH  progesterone challenge  FSH  if high  karyotype </li></ul></ul>
    25. 25. Negative Pregnancy.test TSH ,PROLACTIN, Progesterone challenge test withdrawal bleeding without withdrawal bleeding hypoestrogenic compromised outflow tract +ve.est/progest challenge test -ve.est/progest challenge test FSH>30-40 Normal FSH HSG OR hysteroscopy Asherman’s FSH norm . repeat Repeat+serum estrogen level PreOvFailure hypothalamic-pituitary failure anovulation
    26. 26. Secondary Amenorrhea <ul><li>Treatment goals </li></ul><ul><ul><li>Discovery and treatment of underlying disorder </li></ul></ul><ul><ul><li>Hormone replacement </li></ul></ul><ul><ul><li>Menses every 1-3 months </li></ul></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><ul><li>Ovulation induction </li></ul></ul></ul><ul><ul><ul><li>GnRH pump </li></ul></ul></ul><ul><ul><ul><li>FSH/LH </li></ul></ul></ul>
    27. 27. Amenorrhea <ul><li>26 yo Gravida 0 with menarche at age 14 presents with one-year history of amenorrhea. </li></ul>
    28. 28. Amenorrhea <ul><li>Sexually active, using condoms </li></ul><ul><li>No recent change in weight, skin, hair </li></ul><ul><li>Occasional heat intolerance </li></ul><ul><li>No cyclic pain </li></ul><ul><li>No gynecologic surgery </li></ul><ul><li>Regular menses (every 28-30 days) prior to past year </li></ul>
    29. 29. Amenorrhea <ul><li>Exam </li></ul><ul><ul><li>Overweight </li></ul></ul><ul><ul><li>No galactorrhea </li></ul></ul><ul><ul><li>Normal hair distribution </li></ul></ul><ul><ul><li>Normal pelvic exam </li></ul></ul><ul><li>Pregnancy test </li></ul><ul><li>Progestin challenge, TSH, serum prolactin </li></ul><ul><li>Estrogen/progestin cycle, FSH </li></ul>
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