Lecture 6: Puberty, Disorders of Development, Menstrual Disorders I & II Flashcards
In evaluating a female pt with hyperandrogenism what should be suspected if the total testosterone is >200 ng/dL?
Ovarian androgen producing tumor
List 6 underlying etiologies responsible for hypogonadotropic hypogonadism (FSH + LH <10 mIU/mL).
- Constitutional (physiologic) delay
- Kallmann syndrome
- Anorexia/extreme exercise
- Pituitary tumors/disorders
- Hyperprolactinemia
- Drug useb
What are 3 anatomic causes of delayed puberty in girls?
- Mullerian agenesis
- Imperforate hymen
- Transverse vaginal septum
If a progesterone challenge test (PCT) is negative, what are the next tests to do and what does a positive vs. negative result mean?
- Next do an estrogen/progesterone challenge test –> takes 21 days
- Negative = outflow tract obstruction
- Positive = indicates abnormality w/ the H-P axis or ovaries
What is the definition of secondary amenorrhea?
Pt w/ prior menses has absent menses for 6 months or more
If a progesterone challenge test (PCT) is negative and a estrogen (PCT) test is positive, what levels should be checked next?
FSH and LH levels
What is seen in McCune-Albright syndrome (Polyostotic fibrous dysplasia)?
- Multiple cystic bone defects
- Café au lait spots (face, neck, shoulder and back)
- Adrenal hypercortisolism
What is the mean blood loss per menstrual period; how much loss is associated with anemia and what is a normal and abnormal amount of pad changes per day?
- Mean blood loss is 30cc; changing pads 3-6x per day
- >80cc is assoc. w/ anemia; changin pad q 1-2 hrs is considered excessive
How is true isosexual precocious puberty treated pharmacologically; what is the important of treating this condition?
- Use a GnRH agonist (leuprolide acetate) —> will suppress release of FSH and LH
- If left untreated <50% of girls will not attain an adult height of 5 feet
What is the treatment for abnormal uterine bleeding when massive?
- Hospitalization and transfusions if hemodynamically unstable
- 25 mg IV conjugated estrogens then hormonal tx (Mirena)
What is the effect of elevated insulin and androgen levels in pt’s with PCOS?
↓ the hepatic prod. of sex hormone binding globulins —> ↑ in circulating testosterone
What are the 2 major subgroups of precocious puberty?
- Heterosexual: development of secondary sex characteristics opposite those anticipated –> virilizing neoplasms, CAH, exposure to exogenous androgens
- Isosexual: premature sexual maturation that is appropriate for the phenotype of the affected individual
After hx and PE of patient with primary amenorrhea what do you check for next and how does this dictate the rest of your work-up?
- Check for secondary sexual characteristics
- If present then perform ultrasonography of uterus
- If absent, measure the FSH and LH levels
Although the presentation of sx’s will be similar btw imperforate hymen and transverse vaginal septum, what is one difference?
Transverse vaginal septum will NOT have vaginal bulge
What is responsible for causing atresia of all but 1 follicle during the follicular phase - leading to selection of the dominant follicle; what does the dominant follicle produce?
- ↓ FSH levels progressively cause atresia of all but 1 follicle
- The dominant follicle produces high levels of estradiol
What are 2 causes of outflow tract obstruction in pt w/ primary amenorrhea w/ secondary characteristics and a normal uterus on US?
- Imperforate hymen
- Transverse vaginal septum
List 3 medications which can impair coagulation and may be associated with heavy bleeding?
- Warfarin
- Aspirin
- Clopidogrel
What is the most common cause of primary amenorrhea in women with normal breast development?
Mayer-Rokitansky-Kuster-Hauser Syndrome (Mullerian agenesis)
The corpus luteum produces copious amounts of which hormone?
Progesterone and some estradiol
What are the stages of normal pubertal development from earliest to latest?
- Thelarche
- Adrenarche
- Peak Growth/height velocity
- Menarche
- Mature sexual hair and breasts
*** TAG ME ****
What is the leading cause of female anovulatory infertility?
Polycystic ovarian syndrome (PCOS)
In evaluating a female pt with hyperandrogenism what should be suspected if the DHEA-S levels are >7000 ng/mL?
Adrenal androgen producing tumor
List 4 labs that should be ordered for patient with secondary amenorrhea?
- Urine hCG (ALWAYS!!!)
- TSH
- Prolactin
- FSH
Which disorder of coagulation may be associatd with heavy menstrual flow/AUB?
Von Willebrand disease
Briefly describe the 5 Tanner stages of pubic hair development.
- Stage 1: absence of pubic hair
- Stage 2: sparse hair along labia; hair downy w/ slight pigment
- Stage 3: hair spreads sparsely over jct. of pubes; hair is darker + coarser
- Stage 4: adult-type hair, there is no spread to medial thigh
- Stage 5: spread to medial thighs assuming inverted triangle pattern
Which test can be administered clinically to diagnose true isosexual precocious puberty; what are you looking for?
- Administration of exogenous GnRH (stimulation test)
- Look for resultant ↑ in LH levels consistent w/ older girls who are undergoing normal puberty
What are 2 causes of hyperprolactinemia (>100 ng/mL)?
- Pituitary adenoma
- Empty sella syndrome
Hypergonadotropic hypogonadism (FSH >30 mIU/mL) is a cause of delayed puberty associated with what disease in females?
Gonadal dysgenesis (Turner Syndrome)
Tx for androgen insensitivity syndrome (46,XY)?
- Gonadectomy after puberty to avoid neoplasm (gonadoblastoma and dysgerminomas)
- Can create neovagina by surgical and non-surgical methods
- +HRT
Congenital anomalies of the uterus or vagina are often associated with abnormalities of which organ, how should this be assessed?
- Renal abnormalities
- Assess urinary system w/ an intravenous pyelogram
Diagnosis of menopause is made by looking at levels of what?
↑ FSH since ovary is no longer receptive to FSH there is no negative feedback on the anterior pituitary
What is the invariant mean weight an adolescent needs to be or above to start menarche?
48 kg (106 lbs.)
What is the most common sx of hyperprolactinemia?
Galactorrhea = spontaneous flow of milk from breast
Diagnosis of PCOS needs to meet 2 of which 3 criteria?
- Oligomenorrhea or amenorrhea
- Biochemical or clinical signs of hyperandrogenism: LH to FSH (2:1)
- U/S revealing multiple small cysts beneath cortex of the ovary
Define menorrhagia, metrorrhagia, and menometrorrhagia.
- Menorrhagia = excessive and/or prolonged bleeding (>80 mL and >7 days) occurring at normal intervals
- Metrorrhagia = irregular episodes of uterine bleeding
- Menometrorrhagia = heavy and irregular uterine bleeding
What is the PALM-COEIN classification system for abnormal bleeding in reproductive aged women?
- Polyps - Coagulopathy
- Adenomyosis - Ovulatory dysfunction
- Leiomyoma - Endometriosis
- Malignancy and hyperplasia - Iatrogenic
- Not yet classified
Production and differentiation of which adrenal cortex zone are the initial endocrine changes assoc. w/ puberty?
- Adrenal androgen (DHEA, DHEA-S, and androstenedione) production
- Differentiation by the zona reticularis
- Causes growth of axillary and pubic hair (adrenarche or pubarche)
The endometrial linin?g reaches its maximal thickness during which phase?
Secretory phase
What is the most common cause of primary amenorrhea with absence of secondary sexual characteristics?
Constitutional (physiologic) delay
If karyotype of pt with hypogonadotropic hypogonadism comes back with a Y chromosome, what is the next best step?
Gonadectomy to prevent malignant neoplastic transformation
Why is acanthosis nigricans a common finding in women with PCOS?
Due to the ↑ insulin resistance and hyperinsulinemia
What is the karyotype and characteristics of Mayer-Rokitansky-Kuster-Hauser Syndrome?
- 46,XX —> female range of testosterone
- Absent uterus and upper vagina; renal abnormalities common
- Normal ovaries, secondary development, and external genitalia
- Failure of mullerian ducts to fuse distally
What are some of the treatment options for PCOS?
- Oral contraceptives –> suppress FSH and LH –> ↓ testosterone and estrogen will ↑ SHBG
- Weight loss
- Clomiphene citrate can induce ovulation
- Ovarian diathermy/laser tx
- Spironolactone and/or electrolysis
- Metformin = insulin-sensitizing agent
Puberty is considered delayed in what 4 situations?
- Secondary sexual characteristics have not appeared by age 13
- Thelarche has not occurred by age 14
- No menarche by age of 15-16
- When menses has not begun 5 years after onset of thelarche
Define primary amernorrhea.
- No menstruation by 13 y/o WITHOUT secondary sexual development.
OR
- By the age of 15 y/o WITH secondary sexual characteristics
Which layers of the endometrium remains relatively unchanged during ach cycle and after menstruation provides stem cells for the renewal of the functionalis?
Inner portion or basalis
Define polymenorrhea and oligomenorrhea?
- Polymenorrhea = abnormally frequent menses at intervals <21 days
- Oligomenorrhea = menstrual cycles occuring >35 days but less than 6 months
What is the karyotype seen w/ androgen insensitivity syndrome and what are some characteristics seen in females with this disorder?
- 46,XY —> will have male levels of testosterone
- External female genitalia w/ absent to sparse pubic hair
- Absent uterus and upper vagina
- Breast development w/ smaller than normal areola/nipples
What should you suspect in adolescents that present complaining of monthly dysmenorrhea without vaginal bleeding; a vaginal bulge and midline cystic mass?
Imperforate hymen
Which disease is associated with pseudoisosexual precocity due to sex cord tumors that secrete estrogen, GI polyposis, and mucocutaneous pigmentation?
Peutz-Jeghers syndrome
How does obesity vs. a malnourished adolescent affect the onset of puberty?
- Obese children have earlier onset of puberty
- Malnourished, chronically ill w/ weight loss will have later onset
Which type of precocity results in increased estrogen levels and causes sexual characteristic maturation without activation of H-P-O axis?
Pseudoisosexual precocity
What is the treatment for abnormal uterine bleeding when moderate amount of blood?
Combination OCP’s, Mirena
Which scale can be used as a scoring system for Hirsutism?
Ferrima-Galloway scale
If a pt has primary amenorrhea with secondary sexual characteristics, but an ultrasound reveals an absent or abnormal uterus, what test is done next and what are you looking for?
- Karyotype analysis
- 46, XY = Androgen insensitivity syndrome
- 46, XX = Mullerian agenesis
What is the length of most normal menstrual cycles during the first gynecologic year and how does this change as more cycles occur?
- Often irregular in adolescents, most normal cycles range from 21-45 days
- By the 3rd year after menarche, majority of cycles are 21-35 days
Which test is done clinically in pt with seconary amenorrhea and normal TSH/prolactin; what is a positive and negative test?
- Progesterone challenge test (PCT) —> takes 7-10 days
- Positive PCT = bleeding –> normogonadotropic hypogonadism; most commonly due to PCOS
- Negative PCT = no withdrawl bleeding; indicates inadequate estrogenization or an outflow tract abnormality
Precocious puberty is 5x more likely in which gender?
Girls
Kallman syndrome is due to mutations of the KAL gene on the x chromosome which prevents what; these patients will often have what sx’s?
- Prevents migration of GnRH neurons into hypothalamus
- Causes hypogonadotropic hypogonadism
- Pt’s will often have anosmia or hyposmia (absent or ↓ sense of smell)
Which hormones are required for thelarche (breast development) vs. pubarche/andrenarche (pubic/axillary hair developement)?
- Thelarche requires estrogen
- Pubarche/adrenarche requires androgens
If an estrogen/progesterone challenge test is negative, but there is elevated FSH and LH, this indicates the abnormality is where?
Ovarian
What does LH vs. FSH stimulate in the ovarian follicle?
- LH stimulates Theca cells to produce androgens (androstenedione and testosterone)
- FSH stimulates Granulosa cells to convert androgens –> estrogens (E1 and E2)
Briefly describe the 5 Tanner stages of breast development.
- Stage 1: preadolescent elevation of papilla only
- Stage 2: breast bud stage; small mound w/ enlargement of areolar region
- Stage 3: more enlargin of breast + areola w/o separation of their contours
- Stage 4: projection of areola and papilla to form secondary mound
- Stage 5: mature stage; projection of papilla only, recession of areola to general contour of breast
If a CNS disorder is suspected to be the cause of true isosexual precocious puberty, what is used to diagnose?
MRI of head
