menstruation

Question 1

primary amenorrhea:

Answer 1

-absence of menarche by age 15

Question 2

secondary amenorrhea:

Answer 2

absence of menses for 6 mo or greater in a woman previously menstruating

Informally: denotes any missed menses in a woman previously menstruating

Question 3

Dysfunction of any part of the HPO axis can cause amenorrhea.

Answer 3

Often it’s useful to think about causes as

• Hypothalamic
• Pituitary, or
• Uterine/vaginal in origin.

Question 4

Primary amenorrhea etiology:

Answer 4

Chromosomal abnormalities 
Structural abnormalities:
-Absence of the uterus, cervix, and/or vagina 
-Transverse vaginal septum or imperforate hymen
Hypothalamic causes
Pituitary causes
Ovarian causes
Other

Question 5

most common chromosomal cause of amenorrhea:

Answer 5

Turner syndrome

Question 6

45, XO aka turners:

Answer 6

1/2500 live births, but…

99% of 45, XO conceptions are lost prior to birth, usually in the first or second trimester

Question 7

Turner syndrome includes:

Answer 7

• short stature
• infertility
• primary gonadal failure
• osteoporosis

Question 8

Turner Syndrome and amenorrhea:

Answer 8

Ovaries are replaced by fibrous tissue (“streak gonads”)
Little or no estrogen production is possible
Managed with hormone replacement starting in teens
Normal uterus and vagina are usually present
Pregnancy possible with donated egg, IVF

Question 9

Mosaic turners:

Answer 9

only missing X chromosome in some cells.

• soft signs of turners
• risk for premature menopause

Question 10

Mullerian abnormalities:

Answer 10

Remember that the paramesonephric ducts fuse to form the primordial uterovaginal tissue, and subsequently the fallopian tubes, uterus and upper 1/3 of the vagina

-can cause amenorrhea by causing absence of uterus, cervix or vagina

Question 11

Mayer-Rokitansky-Kuster-Hauser syndrome:

Answer 11

uterus does not fully develop and undeveloped vaginal canal

Question 12

Transverse vaginal septum:

Answer 12

the result of abnormal apoptosis of the vaginal plate.

Can occur at multiple levels.

This can involve both Mullerian tissue and Urogenital (external genitalia) tissue.

Question 13

Imperforate hymen:

Answer 13

Absence of appropriate apoptosis of the cells of the hymenal membrane, which originates from cells of the urogenital sinus (external tissue).
This finding is more common than Mullerian abnormalities, and can be partial or complete.

risk of hematometra or hematocolpos (blood back up into abd) is possible

Question 14

presentation of structural causes of primary amenorrhea:

Answer 14

Congenital anomalies of the uterus and vagina present with cyclic pelvic pain, possible pelvic mass if functional endometrium is present.
If uterus, endometrium are absent then patient will be asymptomatic except for amenorrhea.

Question 15

Management of structural causes of primary amenorrhea:

Answer 15

Resection if it’s an imperforate hymen, vaginal septum
Hysterectomy for absent cervix
Creation of neovagina if necessary

Question 16

Hypothalamic causes of amenorrhea:

Answer 16

Functional hypothalamic amenorrhea
Hypothalamic malfunction due to significant physical or psychological stressors, e.g.:
-Eating disorders (e.g. anorexia nervosa)
-Vigorous exercise 
-Very low body fat
-High emotional or physical stress
Treat by:
- addressing behavioral issues/stressors
-hormone supplementation
-Weight gain if indicated

or

Kallmann syndrome

or

Infiltrative dz and tumors of hypothalamus

Question 17

Kallmann syndrome:

Answer 17

congenital GnRH deficiency classically associated with anosmia
also associated with decreased tanner staging

• manage with E/P therapy
• GnRH can be used to induce ovulation

Question 18

Pituitary causes of primary amenorrhea:

Answer 18

Hyperprolactinemia due to pituitary adenoma
May be associated with galactorrhea
This is more likely to present as secondary amenorrhea– will discuss later

Question 19

Ovarian causes of primary amenorrhea

Answer 19

PCOS
Premature ovarian failure
These also are more likely to present as secondary amenorrhea

Question 20

Androgen insensitivity syndrome (“testicular feminization”)

primary amenorrhea

Answer 20

46 XY karyotype with nonfunctional androgen receptors
Female phenotype
Genetic mutation causes severe impairment in androgen receptor function
Testes may be present in labia
No internal female organs (vagina, cervix, uterus, ovaries)
Removal of gonads after puberty recommended due to risk of malignant transformation

Question 21

primary amenorrhea work-up:

Answer 21

History
General health status (neonatal and childhood)
Pubertal milestones
Change in weight
Exercise habits
Medication history
Family history
Physical exam
Height and weight
Skin 
Breast development
Pelvic examination (or rectal examination) to detect pelvic organs, masses
Syndromic features
Ultrasound may be needed to confirm presence or absence of ovaries, uterus, cervix, testes
Diagnosis
Labs 
If uterus/vagina present:
B-HCG, FSH, karyotype if FSH elevated, prolactin
If uterus is absent
Karyotype, serum testosterone

Question 22

*** most common cause of secondary amenorrhea?

Answer 22

pregos

Question 23

excluding pregnancy from secondary amenorrhea:

Answer 23

Serum measurement of B-hCG is the most sensitive test for pregnancy
The only way to exclude pregnancy is by a pregnancy test
Don’t take sexual history at face value

Question 24

Most common etiologies of secondary amenorrhea:

Answer 24

Ovarian and then hypothalamic

Question 25

Secondary Amenorrhea can be iatrogenic! | medication induced amenorrhea:

Answer 25

``` Hormonal contraceptives Progestin IUD Metoclopramide (Reglan) Causes hyperprolactinemia Antipsychotic drugs (e.g. Thorazine, Haldol, Risperdal) Cause hyperprolactinemia; see above ```

Question 26

Hypothalamic causes of secondary amenorrhea:

Answer 26

Functional hypothalamic amenorrhea (see prior slides) Decreased GnRH secretion commonly associated with anorexia nervosa, low body weight, low body fat, excessive exercise, emotional stress, acute severe illness Risk of osteoporosis due to low estrogen levels Infiltrative lesions of the hypothalamus Lymphoma, sarcoidosis, etc. Celiac disease Nutritional deficiency can impact hypothalamic function

Question 27

Pituitary causes of secondary amenorrhea:

Answer 27

Pituitary Adenomas 90 % are prolactinomas 10% other pituitary masses and disease Thyroid: hyper or hypo can cause it through interactions with pituitary

Question 28

Ovarian causes of secondary amenorrhea:

Answer 28

``` Polycystic ovarian syndrome (PCOS) Cause of 20% of amenorrhea Associated with hyperandrogenism, infrequent or absent menses, polycystic ovaries on ultrasound , obesity Diagnosis of exclusion You’ll have a lecture on this. ``` Premature ovarian failure (primary ovarian insuffiency) Depletion of functional oocytes before age 40 Causes: genetic, autoimmune, cancer treatment, unknown

Question 29

secondary amenorrhea and uterine disorders:

Answer 29

Asherman’s syndrome Acquired scarring of the endometrial lining, due to prior surgery or intrauterine infection See yesterday’s lecture

Question 30

Diagnosing secondary amenorrhea:

Answer 30

-* first B-hCG to rule out prego -History Stress Weight loss / changes in diet Exercise Medications Acne, hirsutism, voice changes Headaches, vision changes, polydipsia, polyuria Hot flashes, vaginal dryness, disturbed sleep Galactorrhea History of uterine surgery or infection -Physical exam Height, weight BMI >30 suspect PCOS <18.5 suspect functional hypothalamic amenorrhea Skin (acne, hirsutism, striae, vitiligo, etc) Breasts (galactorrhea) Pelvic exam (signs of estrogen deficiency) -Labs: B-hCG Prolactin FSH TSH Serum testosterone (if signs of androgen excess)

Question 31

A useful tool: the Progestin withdrawal test

Answer 31

Provera 10 mg/d x 10 d, then stop. Withdrawal bleeding indicates presence of estrogen Failure to bleed indicates inadequate estrogen or endometrial scarring If no menses occurs: Supplement with estrogen, then repeat progestin withdrawal. No bleeding indicates Asherman’s syndrome Bleeding indicates an intact uterus/endometrium that is not receiving estrogen/progesterone– POF, hypothalamic amenorrhea, etc

Question 32

For functional hypothalamic amenorrhea:

Answer 32

Lifestyle changes (adequate caloric intake, moderate exercise, stress reduction) Intervention for eating disorders Consider combined OCs for osteoporosis prevention

Question 33

For Hyperprolactinemia:

Answer 33

``` Dopamine agonist (cabergoline, bromocriptine) Surgery for selected macroadenomas (large, poor response to medication) ```

Question 34

For Premature Ovarian Failure:

Answer 34

Estrogen/progestin therapy to prevent bone loss, manage menopausal sxs

Question 35

For Asherman’s syndrome:

Answer 35

Hysteroscopic lysis of adhesions | Long-term estrogen supplementation for endometrial growth

Question 36

primary Dysmenorrhea:

Answer 36

Pelvic pain that occurs during menstruation in the absence of pelvic pathology

Question 37

Secondary dysmenorrhea:

Answer 37

Pain with menses that results from pathologic changes in the pelvic viscera

Question 38

Primary Dysmenorrhea

Answer 38

Begins with the onset of regular ovulatory cycles (usually 1-3 years post-menarche) Cramps may be accompanied by nausea, vomiting, diarrhea, back pain, headache, dizziness Symptoms start just prior to flow onset and may last several days Present in 60% of teens 15% will seek medical attention

Question 39

what is primary dysmenorrhea caused by?

Answer 39

Caused by excess production of endometrial prostaglandins Increased uterine contractions Dysrhythmic or tetanic uterine contractions Increased uterine muscle tone GI tract stimulation

Question 40

dx of primary dysmenorrhea:

Answer 40

Get a thorough medical history; rule out other pathologies Age at menarche Details of menstrual cycles (frequency, regularity, duration) LMP Onset and duration of cramps Presence of associated sxs (nausea, vomiting, headache, etc) Severity / impact on daily activities Treatment history Sexual history, especially hx of STIs

Question 41

You need to include a pelvic exam if:

Answer 41

Sxs are severe Pt is sexually active Pelvic exam can be omitted if pt is not sexually active and symptoms are mild Transabdominal ultrasound may be a useful alternative to rule out other pelvic/ abdominal pathologies

Question 42

Managing primary dysmenorrhea:

Answer 42

NSAIDs, NSAIDs, NSAIDs! Ibuprofen, naproxen, mefenamic acid Start with onset of menses, continue until sxs abate May need to start 1-2 days prior to menses if sxs severe May need maximum dosage (e.g. ibuprofen 800 mg q8h) Take with food to minimize GI upset -because NSAID are antiprostaglandins

Question 43

what do you do if nsaids for dysmenorrhea don't work or if pt is sexually active?

Answer 43

``` Combined OCP’s If NSAIDs fail or are not tolerated, OR in a sexually active patient! Suppression of ovulation decreases prostaglandin production Long-term use decreases menstrual flow Allows for scheduled or deferred menses Modality of choice if patient is sexually active -can combine with NSAIDs -if failed rule out secondary causes ```

Question 44

Watch for these “Red flags” of primary dysmenorrhea – should warn you that it may be deeper than initially thought…

Answer 44

``` Failure to improve with NSAIDs + OCs Symptoms that worsen on treatment Onset of sxs with menarche (rather than 1-2 y later) Pelvic pain outside of menses History of STI Consider referral for laparoscopy ```

Question 45

secondary dysmenorrhea etiologies:

Answer 45

``` Endometriosis Adenomyosis Uterine leiomyomata Ovarian cysts Pelvic adhesions Chronic PID Obstructive uterovaginal anomalies Cervical stenosis Copper IUD IBS Inflammatory bowel disease Interstitial cystitis ```

Question 46

secondary dysmenorrhea diagnostic clues:

Answer 46

The prevalence of secondary dysmenorrhea increases with age | The prevalence of primary dysmenorrhea decreases with age, and may remit after a term pregnancy

Question 47

suggestive hx of secondary dysmenorrhea:

Answer 47

``` Onset after age 25 Abnormal uterine bleeding Non-midline pelvic pain Absence of other menstrual sxs (nausea, vomiting, headache, etc.) Presence of dyspareunia or dyschezia Progressive sxs ```

Question 48

diagnosis of secondary dysmenorrhea:

Answer 48

Pelvic exam findings are critical Purulent cervical discharge Cervical motion and/or adnexal tenderness Nodularity of uterosacral ligaments Uterine enlargement or irregularity Adnexal mass Pelvic ultrasound may be useful to clarify above findings Labs- screen for G/Chl -laparoscopy or hysteroscopy may be needed

Question 49

management of secondary dysmenorrhea:

Answer 49

``` NSAIDs, analgesics, etc. OCs, medicated IUD Treat the underlying disorder, e.g. Antibiotics for pelvic infection Cautery of endometrial implants Hormonal tx for endometriosis Resection of symptomatic fibroids Ovarian cystectomy Hysterectomy Drug tx for inflammatory bowel disease Drug tx for interstitial cystitis ```

Question 50

Menorrhagia:

Answer 50

prolonged and or heavy menses | - blood loss >80 ml

Question 51

prolonged menses:

Answer 51

>7 days

Question 52

metrorrhagia:

Answer 52

irregular bleeding, especially between menses

Question 53

menometrorrhagia

Answer 53

excessive and irregular uterine bleeding

Question 54

dysfunctional uterine bleeding (DUB)

Answer 54

Abnormal bleeding not from anatomic abnormality, generally anovulatory bleeding.

Question 55

polymenorrhea

Answer 55

-cycle length less than 24 days

Question 56

DUB causes:

Answer 56

Common in adolescence, perimenopause, PCOS, thyroid disorders

Question 57

Anatomic abnormalities

Answer 57

Endometrial polyp Uterine leiomyomata, especially submucosal Adenomyosis Uterine malignancy