Amenorrhea: OMED, UWise

Woman hasn't had period in 6 months -- had some surgery before. Diagnosis?

(1) *Asherman's Syndrome* Dilation/Curettage --> scarring --> nonresponsive endometrium -or- (2) *Ablation* worked Just see surgical history

15 year old girl, no periods. NBS?

(1) Look at breasts - for hormones (2) Ultrasound uterus - for anatomy

Woman hasn't had periods in 6 months. Has milky discharge from nipples. NBS?

(1) Measure prolactin --> likely elevated (2) Do MRI and check meds (distinguish prolactinoma from med induced)

15 year old girl, no periods. Has breasts Ultrasound: no uterus Differential? NBS?

(1) Mullerian agenesis (2) Androgen insensitivity NBS: Differentiate the two by karyotype and testosterone levels

What can cause a woman to miss one period?

(1) Pregnancy (2) Stress

Girl is 15 no periods, has no/weird breasts but ultrasound shows normal uterus. Differential?

(1) Turner syndrome (2) Kallman syndrome (3) Craniopharyngioma

How to work up secondary amenorrhea?

(1) Urine pregnancy test (positive -- pregnant) (2) TRH/TSH (high -- hypothyroidism) (3) Prolactin (high -- prolactinoma or meds) --> MRI (tumor -- prolactinoma)

When should a girl develop breasts, hair?

(secondary sexual characteristics) 13 yrs old

Consequences of Kallman syndrome?

- Anosmia - Low GnRH - Low FSH/LH - Low estrogen, progesterone

How do you evaluate primary amenorrhea?

- Look at "anatomy" and "hormones" - Good anatomy = there's a uterus - Good hormones = there are breasts AND ovaries

What are the consequences of mullerian agenesis? How are the hormones?

- No periods - Infertility

What are the consequences of androgen insensitivity syndrome?

- No periods - Infertility - Has breasts - Has testes not ovaries - Risk for testicular cancer

Consequences of craniopharyngioma?

- Smell is GOOD - Low GnRH - Low FSH/LH - Low estrogen, progesterone

What are the consequences of Turner syndrome? (appearance/breasts, hormone levels, anatomy, fertility)

- Webbed neck - Wide nipples, barrel/shield chest - Estrogen, progesterone low - FSH, LH high - Vagina, uterus, fallopian tubes present - Infertility

When should a girl have periods? What is it called if she doesn't get periods by then?

15 yrs old Primary amenorrhea

A 17-year-old nulliparous female is brought in by her mother because she has not yet had any menses. She is otherwise in good health, but recently has been experiencing cyclical lower abdominal cramping. She has never had sexual intercourse. She is 5 feet 6 inches tall and weighs 120 pounds. On examination, her breasts are Tanner Stage IV. She has some suprapubic tenderness on abdominal exam. Her pelvic exam reveals normal external genitalia, but there was difficulty inserting a speculum due to patient's discomfort. Beta-hCG < 5 mIU/mL. What is the most likely diagnosis in this patient? A. Genital tract outflow obstruction B. Müllerian agenesis C. Hypothalamic-pituitary dysfunction D. Psychogenic amenorrhea E. Constitutional delay in menarche

A This patient's primary amenorrhea, with normal secondary sexual characteristics, development and cyclical abdominal pain, points to an anatomical cause of amenorrhea, which is preventing menstrual bleeding. An imperforate hymen commonly causes this and the treatment is surgical. In Mϋllerian agenesis, or Mayer-Rokitansky-Kϋster-Hauser syndrome, there is congential absence of the vagina and usually an absence of the uterus and fallopian tubes. Ovarian function is normal and all the secondary sexual characteristics of puberty occur at the appropriate time.

What are the causes of primary amenorrhea(8)? Three categories

A) Anatomy bad, hormones good. (1) Mullerian agenesis (2) Androgen insensitivity B) Anatomy good, hormones bad (1) Craniopharyngioma (2) Kallman's Disease (3) Turner's Syndrome C) Anatomy good, hormones good (a) Imperforate hymen (b) Anorexia/weight loss (c) Pregnant before period

15 year old girl no periods has breasts but ultrasound shows no uterus. Karyotype XY and testosterone is high.

Androgen insensitivity syndrome

A 42-year-old G0 woman presents to the office for a health maintenance examination. She reports that her menses have been irregular her entire life ever since menarche at age 15, occurring every 20-45 days. She is not sexually active and reports no other medical problems. She smoked for two years during her adolescence. She has a family history of cervical cancer affecting her mother at age 42. On examination, she is 5 feet 4 inches tall and weighs 180 pounds (BMI 31). She has noticeable hair growth on her upper lip and chin. The rest of her examination including a pelvic examination is normal. Compared to the general population, which of the following malignancies is she at increased risk for developing? A. Breast B. Endometrial C. Cervical D. Lung E. Colorectal

B. This patient most likely has polycystic ovarian syndrome (PCOS), with her clinical manifestation of oligo-menorrhea, obesity, and hirsutism. Because of the chronic unopposed estrogen exposure that accompanies women with PCOS, these individuals carry a higher risk of developing endometrial hyperplasia and cancer. Although obesity in postmenopausal women is associated with a higher risk of breast cancer, it does not increase the risk in premenopausal women. PCOS is considered to increase the risk of ovarian cancer. She does not have obvious risk factors for cervical cancer, lung, or colon cancer, but should be screened and counseled accordingly based on usual guidelines.

How are the breasts in mullerian agenesis? Why?

Breasts are NORMAL because ovaries are NORMAL (hormone levels are good)

Woman hasn't had periods in 6 months --> not pregnant, TSH normal, MRI shows mass. Breast discharge. What do you NEVER give?

Bromocriptine or cabergoline (too many side effects!)

A 24-year-old nulliparous woman comes into the office because she has not had her menses for six months. She is in good health and not taking any medications. She is not sexually active. She does well in graduate school, despite her demanding new program. Her height is 5 feet 6 inches and her weight is 104 pounds. Her vital signs are normal. Her physical examination, including a pelvic examination, is completely normal. What is the most likely reason for her amenorrhea? A. Ovarian dysfunction B. Thyroid disease C. Premature ovarian failure D. Hypothalamic-pituitary dysfunction E. Pregnancy

D Anorexia nervosa or significant weight loss may cause hypothalamic-pituitary dysfunction that can result in amenorrhea. A lack of the normal pulsatile secretion of gonadotropin releasing hormone (GnRH) leads to a decreased stimulation of the pituitary gland to produce follicle stimulating hormone (FSH) and luteinizing hormone (LH). This leads to anovulation and amenorrhea. Although testing for thyroid dysfunction may be indicated, she has no other symptoms to suggest thyroid disease. While ovarian dysfunction/failure, premature ovarian failure and pregnancy cause amenorrhea, they are unlikely in this case.

A 31-year-old G3P0 presents with amenorrhea for six months. She is otherwise in good health and is not taking any medications. She had a miscarriage seven months ago, which was complicated by an infection and required antibiotics and a dilation and curettage procedure. Her examination is normal. Her laboratory results show a Beta-hCG <5 mIU/mL, and normal TSH and prolactin levels. What is the most likely underlying cause of this patient's amenorrhea? A. Chronic endometritis B. Recurrent miscarriages C. Hypothalamic-pituitary amenorrhea D. Asherman's syndrome E. Sheehan's syndrome

D Asherman's syndrome can be caused by curettage or endometritis. The intrauterine synechiae or adhesions result from trauma to the basal layer of the endometrium, which causes amenorrhea. Chronic endometritis may be associated with abnormal uterine bleeding and not amenorrhea. Hypothalamic amenorrhea is unlikely because of the temporal relationship of her amenorrhea to the procedure. Sheehan's syndrome is typically due to severe postpartum hemorrhage leading to pituitary apoplexy.

A 32-year-old nulliparous woman presents with amenorrhea for the last three months. She has a long history of irregular cycles, 26 to 45 days apart, for the last two years. She is otherwise in good health and is not taking any medications. She is sexually active with her husband and uses condoms for contraception. She is 5 feet 4 inches tall and weighs 140 pounds. On exam, she has a slightly enlarged, non-tender uterus. There are no adnexal masses. Which of the following is the most appropriate test to obtain in this patient? A. Thyroid stimulating hormone (TSH) B. Progesterone and estrogen C. Follicle stimulating hormone and luteinizing hormone levels (FSH and LH) D. Urine pregnancy test E. Pelvic ultrasound

D Pregnancy is the most common cause of amenorrhea. It is important to consider it early in the workup to avoid unnecessary tests, procedures and treatments that may be contraindicated during pregnancy. Although the patient has a history of irregular cycles and is using condoms for contraception, it is important to first rule out pregnancy before initiating further work-up.

A 22-year-old nulliparous woman presents with five months of amenorrhea since discontinuing her oral contraceptive pills. She had been on the pill for the last six years and had normal menses every 28 days while taking them. She is in good health and not taking any medications. She is 5 feet 4 inches tall and weighs 140 pounds. Her examination, including a pelvic examination, is normal. Which of the following historical elements would be most useful in determining the cause of amenorrhea in this patient? A. Age at first intercourse B. History of sexually transmitted infections C. Parity D. History of oligo-ovulatory cycles E. Recent history of weight loss

D Since most women resume normal menstrual cycles after discontinuing oral contraceptive pills (OCPs), they are not usually considered the cause of the amenorrhea. A history of irregular cycles prior to pill use may increase the risk of amenorrhea upon discontinuation. This is sometimes referred to as "post pill amenorrhea." A complete work-up should be performed to properly find the cause. Although the other historical elements are all important components of a complete gynecological history, they are not helpful to find the etiology of amenorrhea in this patient. Significant weight loss might cause amenorrhea; however, this patient still has normal body mass index, which makes it unlikely cause of amenorrhea.

A 23-year-old nulliparous woman presents to the office because she has not had any menses for four months. She has a long history of irregular menstrual cycles since menarche at age 14. She is otherwise in good health and is not taking any medications. She is thin and has chronic anxiety. Her Beta-hCG is < 5 mIU/mL, and her prolactin and TSH levels are normal. What would be the next best diagnostic test to order? A. Estrogen level B. Progesterone level C. Gonadotropin releasing hormone level (GnRH) D. Follicle stimulating hormone and luteinizing hormone levels (FSH and LH) E. Dehydroepiandrosterone sulfate (DHEAS)

D The causes of hypothalamic-pituitary amenorrhea are functional (weight loss, obesity, excessive exercise), drugs (marijuana and tranquilizers), neoplasia (pituitary adenomas), psychogenic (chronic anxiety and anorexia nervosa), and certain other chronic medical conditions. In this case, the next step to make a diagnosis is to obtain FSH and LH levels, which would be expected to be in the low range. You already know that her prolactin level is normal, which is consistent with the diagnosis. Prolactin would be elevated with a prolactin-secreting pituitary adenoma.

A 33-year-old nulliparous woman presents with amenorrhea for the past 12 months. She also reports a recent onset of dyspareunia, causing her to feel anxious about having intercourse. She had menarche at age 15. Her cycles were normal until two years ago when she began skipping menses. She is otherwise in good health. She is 5 feet 4 inches tall and weighs 130 pounds. Her physical examination is completely normal. TSH and prolactin levels are normal. Urine pregnancy test is negative. What is the most likely cause of this patient's amenorrhea? A. Psychogenic B. Genital tract outflow obstruction C. Asherman's syndrome D. Premature ovarian failure E. Pituitary adenoma

D The patient's symptom of dyspareunia is likely caused by vaginal dryness, which is associated with estrogen deficiency. Hypergonadotropic amenorrhea is the result of ovarian failure or follicular resistance to gonadotropin stimulation. The history, physical exam and labs make the other possibilities less likely: psychogenic disorder (no chronic anxiety or anorexia nervosa), outflow obstruction (previously had periods), Asherman's syndrome (no history of pregnancy or intrauterine procedures), or a pituitary tumor (normal labs).

Woman hasn't had periods in 6 months --> not pregnant, TSH normal, MRI shows mass. NBS?

Diagnosis: Prolactinoma Don't resect! NBS: Pramipexole, Ropinarole

Woman hasn't had period in 6 months -- she's thin, atheletic, anorexic etc. Treatment?

Estrogen-Progesterone oral contraceptives (OCPs!!!)

Woman hasn't had period in 6 months --> not pregnant, TSH normal, prolactin normal, MRI normal. NBS?

Evaluate for "HARM" Hypothalamus - Asherman syndrome - Resistant Ovary - Menopause -

Woman hasn't had periods in 6 months -- differential?

Evaluate for... (1) Pregnancy (really, you check after 1 month amenorrhea) (2) Hypothyroidism (3) Prolactinoma (4) Dopamine blockers meds (incr prolactin) Note: workup for secondary amenorrhea from hypogonadrotrophic hypogonadism includes hormonal (TSH, prolactin), acquired, congenital (Kallman, craniopharyngioma) Then, evaluate for..."HARM" (1) Hypothalamus (2) Asherman (3) Resistant Ovary Syndrome (4) Menopause

How are testosterone level sin androgen insensitivity syndrome?

HIGH because body isn't responding (testes produces more)

How are the breasts in androgen insensitivity syndrome? How are the ovaries in androgen insensitivity syndrome?

Has breasts b/c no response to androgens NO ovaries -- has TESTES because originally XY

Woman hasn't had periods in 6 months, FSH/LH are super high, estrogen/progesterone are low, ultrasound shows follicles in ovaries. NBS?

Hormone replacement therapy -- give estrogen

What is Kallman syndrome?

Hypothalamus doesn't work -- no GnRH and anosmia

What is craniopharyngioma?

Hypothalamus mass -- hypothalamus doesn't work so no GnRH However smell is normal

Woman hasn't had period in 6 months -- everything is negative. Diagnosis of exclusion?

Hypothalamus not producing FSH/LH

Woman hasn't had period in 6 months -- lots of weight loss, anorexia. Diagnosis?

Hypothalamus not producing FSH/LH

Woman hasn't had period in 6 months -- she's thin, atheletic, anorexic etc. Diagnosis?

Hypothalamus not producing FSH/LH

Woman hasn't had periods in 6 months --> high TRH or TSH. NBS?

Hypothyroidism --> give levothyroxine (High TRH or high TSH indicates low T3/T4/thyroid hormone --> low thyroid hormone --> prolactin increases)

Girl is 15 no periods, has no/weird breasts but ultrasound shows normal uterus. NBS?

Karyotype (XO = turner) Smell (anosmia = kallman) FSH, LH levels (high = turner, low = craniopharyngioma) MRI (tumor = craniopharyngioma)

Woman hasn't had period in 6 months, she is 40 years old. Diagnosis?

Menopause

Girl is 15 has no periods, breasts are fine, uterus is absent, testosterone is low, karyotype XX. Diagnosis?

Mullerian agenesis

How is diagnosis of mullerian agenesis and androgen insensitivity different?

Mullerian agenesis - XX karyotype, normal testosterone Androgen insensitivity - XY karyotype, high testosterone

What is mullerian agenesis?

Mullerian duct doesn't form -- there's no fallopian tube, no uterus, and no upper 1/3 of vagina

How does menopause happen?

Over time, the ovaries get tired and stop working. They stop producing estrogen and progesterone. FSH and LH get elevated (hypergonadotropic hypogonadism). As ovulation stops, the follicles (eggs) in the ovaries degenerate.

What is androgen insensitivity syndrome?

Patient is XY, but body doesn't respond to androgens/testosterone.

Most common cause of secondary amenorrhea?

Pregnancy -- ALWAYS CHECK!

If woman has missed one period -- NBS?

Pregnancy test

Menopause before 40 years old. Diagnosis?

Premature ovarian failure

Primary Amenorrhea vs Secondary Amenorrhea

Primary amenorrhea - patient is 15 and no periods Secondary amenorrhea - patient had periods which suddenly stopped

HELP. Woman hasn't had period in 6 months -- has super high FSH/LH. Diagnosis?

Resistant ovary syndrome

What's the difference between resistant ovary syndrome and menopause? What tool is used to tell them apart? What hormone changes are in both conditions?

Resistant ovary syndrome - ovary still has its follicles Menopause - ovary loses follicles Use ULTRASOUND to look for ovarian follicles In both: FSH/LH are up, estrogen/progesterone are down

Woman hasn't had periods in 6 months. Diagnosis?

Secondary amenorrhea

Primary Amenorrhea OMED Table

See img

Watch the rest of the online MEDED video for progesterone test workup

Start at 11:00

Woman hasn't had periods in 6 months --> not pregnant, TSH normal, MRI normal, has schizophrenia. Breast discharge. NBS?

Stop schizophrenia drugs -- antipsychotics are dopamine blockers which increase prolactin.

Woman misses period. Having lots of problems in life.

Stress caused missed period -- wait/watch, pregnancy test

What is resistant ovary syndrome?

The ovaries FSH/LH receptors aren't working, so the ovaries don't produce estrogen/progesterone. It's like menopause. FSH and LH get elevated.

Diagnosed with androgen insensitivity syndrome -- NBS?

To ORCHIECTOMY after age 20 to prevent TESTICULAR CANCER

How do you define secondary amenorrhea?

Woman used to have periods, but hasn't had periods in > 6 months.

What is Turner syndrome?

XO karyotype Streak ovaries -- ovaries don't work

A 23-year-old nulliparous woman presents to the office because she has not had any menses for four months. She has a long history of irregular menstrual cycles since menarche at age 14. She is in good health and is not taking any medications. She is sexually active with her partner of six months, and uses condoms for contraception. She is 5 feet 4 inches tall and weighs 170 pounds. On exam, she has noticeable hair growth on her upper lip and chin. The rest of her examination including a pelvic exam is normal. Her Beta-hCG is < 5 mIU/mL, and her prolactin and TSH levels are normal. In addition to recommending weight loss, what is the most appropriate next step in the management of this patient? A. Treatment with gonadotropin releasing hormone level (GnRH) agonist B. Treatment with clomiphene citrate C. Treatment with oral contraceptives D. Check progesterone levels E. Check cortisol levels

C Oral contraceptives (OCPs) are the most appropriate treatment for this patient who most likely has the diagnosis of polycystic ovarian syndrome (PCOS). The constellation of findings support this clinical diagnosis (irregular cycles, obesity, and hirsutism). Because she is using condoms for contraception and is sexually active, OCPs would help regulate her cycles and further provide effective contraception. When she desires pregnancy, however, she will most likely need treatment for ovulation induction due to the anovulatory cycles as the leading cause of her oligomenorrhea. Clomiphene citrate is not indicated at this time.