1
Q
What does STRAW stand for? What is the definition of STRAW?
Does perimenopause last longer than menopausal?
What kind of symptoms do you get near menopause?
A
STRAW (STages of Reproductive Aging)
- Definition: lays out phases of menstrual lifespan (reproductive, menopausal transition, and post-menopause
- Perimenopause may last longer than menopausal transition (involves period before and after last menstrual period)
- Vasomotor symptoms are most likely to occur in late menopausal transition and early post-menopause
2
Q
Define mepopause and give epidemiology.
A
Menopause
- Definition: the final menstrual period (FMP) confirmed after one year of no menstrual bleeding; permanent cessation of menses
- Epidemiology: 51 to 52 y/o
3
Q
What is the physiology of menopause?
A
- Physiology:
- Follicular and oocyte depletion as a women ages due to gene regulated apoptosis and ovulation
- Decrease in estrogen → GnRH activation via feedback mechanism → constant release of LH and FSH → very high serum levels of LH/FSH (specific for menopause)
- Decline in fertility: fertility is near its end at age 42
- Granulosa cells of antral follicles produce AMH → can be used to determine the number of remaining follicles (declines in menopause)
4
Q
What are the symptoms of menopause?
A
- Symptoms:
- Vasomotor symptoms (hot flashes and night sweats), vaginal atrophy, sleep disturbances, psych disturbances (moody attitude), decreased libido
- Hot flashes: narrowing of thermoregulatory zone of brain → body is tricked into thinking the woman is “hot” → hot flashes (dilation of peripheral vessels)
- Vasomotor symptoms (hot flashes and night sweats), vaginal atrophy, sleep disturbances, psych disturbances (moody attitude), decreased libido
5
Q
What are the complications of menopause?
A
- Complications of menopause
- Decreased estrogen → increased LDL/total cholesterol → increased risk of CVD (number one cause of mortality in females age 50+)
- Estrogen has an impact on insulin and glucose metabolism
- Estrogen inhibits the activity of osteoclasts; therefore, in menopause, lack of estrogen is associated with osteoporosis
6
Q
What are hormonal treatments of menopause?
A
- Hormonal tx of hot flashes, vaginal atrophy, and decreased libido: estrogen + progesterone (prevents endometrial hyperplasia)
- Estrogen promotes mucosal water retention, sebaceous gland secretion, and maintains blood flow, acidic pH, and elasticity of vagina
- Lifestyle changes: exercise, keep cool, avoid hot flash triggers (spicy and hot foods), R-E-L-A-X
- For decreased libido: testosterone can also be used
- Contraindications of estrogen replacement therapy: ER+ breast cancer, hx of DVT/PE
7
Q
Define perimenopause and provide epidemiology.
A
Perimenopause
- Definition: transition phase from reproductive phase to post-menopausal phase; most symptomatic period in women’s life
- Begins with varied menstrual cycle that can last >7 days
- Characterized by unpredictable hormone concentrations
- Epidemiology: 34 to 54 y/o lasting 5-6 years (avg: 46 y/o)
8
Q
What are non hormonal treatments of menopause?
A
- Nonhormonal prescriptions that act on CNS (directly on hypothalamus)
- Hot flashes: antidepressants (SSRI/SNRI), hypnotic meds, anticonvulsants (Gabapentin), Antihypertensive (clonidine), neuropathic pain drugs
- Vaginal atrophy: vaginal moisturizers (hydrophilic biofilms that cling to vaginal wall), sexual lubricants, estrogen
9
Q
Define primary ovarian insufficiency and provide symptoms/presentation.
A
Primary Ovarian Insufficiency (aka premature menopause)
- Definition: loss of ovarian function that occurs prior to age 40
- Follicles are still present, but no longer functional
- POI may not be permanent
- Presentation: infertility, menstrual dysfunction, symptoms of estrogen deficiency, sexual dysfunction
10
Q
For primary ovarian insufficiency, provide etiology, risk factors, and treatment.
A
- Etiology: follicular dysfunction (90%), follicular depletion (10%)
- Risk factor: Fragile X carrier status, thyroid dysfunction, adrenal dysfunction
- Treatment: hormone replacement therapy to combat the risks of estrogen depletion
- No treatment to induce ovulation in infertile females with POI, but there is a small chance for spontaneous pregnancy (no chance with menopause)
11
Q
What are the two regions near the pituitary gland? What do they contain?
A
- Regions
- Sellar region: region that includes the pituitary gland
- Parasellar region: regions that includes the optic chiasm and cranial nerves
- Lesions and tumors can affect both regions
12
Q
What are two types of pituitary adenomas? How do each present and how can they be treated generally?
A
- Functioning vs non-functioning: functioning adenomas have hormonal secretions
- Non-functioning pituitary tumors:
- Present with compressive sx, hypopituitarism
- Tx: transsphenoidal hypophysectomy followed w/ radiation
- Non-functioning pituitary tumors:
13
Q
What are the cellular subtypes of pituitary adenomas? What are complications associated with pituitary adenoma?
A
- Subtypes: PLH (prolactin hormone), ACTH, GTH, GH, and TSH
- Complications of pituitary adenoma:
- Hypopituitarism: typically hypersecretion of one hormone and hyposecretion of other hormones due to pituitary compression
- Pituitary apoplexy: hemorrhage of pituitary gland
14
Q
What are two size subtypes of pituitary adenoma and what are they associated with?
A
- Size subtypes: Microadenoma (<1cm), macroadenoma (>1cm)
- Microprolactinoma: no compressive symptoms
- Macroprolactinoma: compressive symptoms (i.e. vision disturbances, facial drooping)
15
Q
What are causes of hyperprolactinemia?
Divide between physiologic and pathologic
A
- Causes of hyperprolactinemia:
- Physiologic: pregnancy (estrogen increases prolactin levels), nipple stimulation, stress, exercise, chest trauma
- Pathologic: decreased dopamine response (due to masses or psych drugs), renal failure (decreased peripheral clearance of prolactin), hypothyroidism (TRH causes increase in prolactin)
16
Q
What are clinical manifestations of hyperprolactinemia and provide mechanism
A
- Clinical manifestations
- Galactorrhea, amenorrhea, decreased libido, headache (compression)
- Increased prolactin → negative feedback on GnRH → decreased LH/FSH → decreased estrogen → infertility, sexual dysfunction, osteoporosis
17
Q
How do you treat prolactinoma?
Provide side effects of drug! Provide a surgery too
A
- Treatment of prolactinoma:
- Dopamine agonist (first line treatment): bromocriptine, cabergoline
- SE of bromocriptine: N/V, postural hypotension on first dose
- Surgery: debulking procedure (if resistant to drugs), radiation therapy (if resistant to drugs/debulking)
- Dopamine agonist (first line treatment): bromocriptine, cabergoline
18
Q
What two things can a growth hormone cell adenoma cause? Describe the clinical manifestations of each!
A
- Growth hormone cell adenoma
- Types
- Gigantism (child form):
- Clinical presentation: increased linear bone growth in children (epiphyses are not fused)
- Acromegaly (adult form):
- Clinical manifestations: enlarged bones of hands/feet/jaw, growth of visceral organs (large heart → failure) enlarged tongue
- Gigantism (child form):
- Types
19
Q
How do you diagnose and treat growth hormone cell adenoma?
A
- Diagnosis: elevated GH (lack of negative feedback by oral glucose) and IGF-1 (insulin growth factor)
- Treatment: octeotride (somatostatin analog à inhibition of GH release), cabergoline (dopamine agonist), pegvisomant (GH receptor antagonist), surgical debulking, radiation treatment (for residual tumor post-surgery or failed drugs)
- Goal is to keep GH < 1.0 ng/mL
20
Q
Define hyppituitarism and proivde diagnostic labs.
A
- Definition of hypopituitarism
- Occurs when >75% of pituitary parenchyma is lost
- Diagnostic labs of hypopituitarism:
- Free T4, testosterone (men), AM cortisol, GH following insulin-induced hypoglycemia, electrolytes
21
Q
What is the etiology of hypopituitarism? Provide a few syndromes and a lot of other diseases.
A
- Etiology of hypopituitarism
- Vascular disorders: pituitary infarction, pituitary apoplexy, aneurysm, vasculitis
- Sheehan’s syndrome: in pregnancy, pituitary gland doubles in size, but blood supply does not increase → pituitary infarction
- Empty cell syndrome: congenital defect of sellar region
- Pathophysiology: herniation of arachnoid and CSF into sellar region → compression → destruction of pituitary gland → empty cell syndrome
- Physical agents: radiation, surgery, head trauma
- CNS insults: meningitis
- Inflammatory/granulomatous diseases: TB, sarcoidosis, histiocytosis, hemochromatosis, hypophysitis
- Idiopathic: GH deficiency, hypogonadotropic hypogonadism
- Vascular disorders: pituitary infarction, pituitary apoplexy, aneurysm, vasculitis
22
Q
What is the etiology, sx, and tx of central diabetes insipidus?
A
- Diabetes insipidus
- Central (ADH deficiency)
- Etiology: all causes of hypopituitarism
- Sx: polydipsia, polyuria, life-threatening dehydration
- Tx: desmopressin (ADH analog), water, treat underlying cause
- Central (ADH deficiency)
23
Q
What is the etiology of nephrogenic diabetes insipidus?
A
- Nephrogenic (ADH resistance)
- Etiology: familial, metabolic (low Ca, high K, lithium, osmotic diuresis, chronic renal disease
24
Q
For the following conditions, provide urine volume, urine osmolarity, serum osmolarity, respose to dehydration, response to exogenous ADH:
- Central DI
- Nephrogenic DI
- Fluid overload
A
25
# Define unintended pregnancy, how many in US are unintended, epidemiology.
What are the two most common contraceptives?
* Unintended pregnancy: defined as a pregnancy that is either unwanted, unplanned, or simply mistimed
* ~50% of pregnancies in the United States are unintended (more than other developed countries)
* Epidemiology: teenagers, unmarried women, black women, sexual minorities, low education/income
* Most common contraceptives: tubal ligation, oral contraceptive pill
26
What are some barriers to effective contraception?
* Barriers to effective contraception:
* Physical ability to use methods, religious contraindications, cost, accessibility, insurance coverage, medical contraindications
27
Provide the MOA of the two hormones involved in contraceptives?
* Progestin (prevents ovulation and fertilization)
* Suppresses LH surge, thickens cervical mucus, reduces ovum motility, thins endometrium
* Estrogen
* Suppresses FSH, potentiates progestin
28
Provide the following generally:
* half-life of each hormone
* where are they metabolized
* which two drugs do not have a rapid return to fertility?
* what is the effect on obese patients?
* What are general side effects of all?
* General pharmacokinetics/pharmacology
* Half-life: estrogen (long), progestin (short
* Metabolism: liver (P450s)
* Return to fertility: rapid except for depo (9-10 months) and Nexplanon (1-2 months)
* Effect in obese patients: Nexplanon and OCPs may be slightly less effective (others are equally effective)
* General side effects: all can cause spotting of blood except copper IUD (can cause heavy bleeding)
29
For Emergency contraception (Plan B/levonorgestrel):
* MOA
* Benefits
* Risks
30
For Fertility awareness methods (calendar, temperature, cervical mucus):
* MOA
* Benefits
* Risks
31
For Barrier methods (condom, cervical cap, diaphragm):
* MOA
* Benefits
* Risks
32
For Progestin only pills (POP):
* MOA
* Benefits
* Risks
33
For Combined hormonal methods (oral contraceptive pill, ring, patch):
* MOA
* Benefits
* Risks
34
For Depot medroxyprogesterone acetate (aka Depo-provera):
* MOA
* Benefits
* Risks
35
For Levonorgestrel implant (nexplanon):
* MOA
* Benefits
* Risks
36
For Copper IUD (ParaGard):
* MOA
* Benefits
* Risks
37
For Levonorgestrel (LNG) intrauterine device (IUD) (mirena, Skyla, kyleena):
* MOA
* Benefits
* Risks
38
For Surgical sterilization (vasectomy, tubal ligation, Essure):
* MOA
* Benefits
* Risks
39
What are the phases of growth from pre natal to adult and what are the main factors that influence growth at each stage?
* Phases of growth: prenatal → infancy (nutrition) → childhood (growth hormone) → adolescence (growth hormone and sex steroids)
40
What are the maternal factors before and after pregnancy that affect prenatal growth of a baby?
* Prenatal growth
* Maternal factors
* Before pregnancy: maternal weight, nutritional status (folate deficiency)
* During pregnancy: poor weight gain, chronic illness (malabsorption/DM/renal disease), poor nutrition, drug use, decreased O2 available to fetus (high altitude, anemia)
41
What are the fetal factors that affect prenatal growth of a baby?
* Fetal factors
* Familial/chromosomal abnormalities, intrauterine infections (i.e. TORCH – most common infections associated with congenital abnormalities)
42
What are the uterine/placental factors that affect prenatal growth of a baby?
* Uterine/placental factors
* Inadequate placental growth, uterine malformations, decreased utero-placental blood flow, multiple gestations
43
For intrauterine growth restriction, provide the definition, epidemiology, and co-morbidities (and why this happens)?
* Intrauterine growth retardation (IUGR)
* Definition: combination of maternal and fetal factors that lead to a fetal weight of less than 10th percentile
* Epidemiology: 20% of stillborn births, higher mortality rates
* Co-morbidities:
* Pathophysiology: decreased placental transfer of nutrients/oxygen →
* Hypoglycemia, hypocalcemia, polycythemia, perinatal asphyxia, hypothermia (low fat storage), thrombocytopenia/leukopenia
44
What are the lasting effects of small birth size via IUGR?
* IUGR can lasting effects into adulthood:
* Small birth size → abnormal glucose/insulin metabolism → increased risk of CVD, diabetes, cognitive disabilities, obesity, and cancers
45
Provide what normal weight gain, normal height gain, and normal growth velocity is?
* Normal growth patterns
* Normal weight gain: babies double birth weight by four months, triple birth weight by one year, ~5 lbs weight gain/per inch height gain
* Normal height gain: half of adult height achieved at 24-30 months, slump in height velocity right before pubertal growth spurt
* Normal growth velocity (rule of fives): 0-1 yr (25cm/yr), 1-4 yrs (10cm/yr), 4 to puberty (5 cm/yr), puberty to adult (10-15cm/yr)
46
How is bone age determined? What bone parts are assessed?
* Bone age: generally use x-ray of left hand → assess epiphysis carpal bones → bone age and predicted adult height
47
When should you be worried about growth?
* Abnormal growth patterns
* When to worry: height \< 3rd percentile, \> 97th percentile OR growth velocity \< 10th percentile, \>95th percentile
48
Provide etiologies of short stature (one big syndrome with sx and tx)?
* Short stature
* Intrinsic short stature
* Familial short stature
* Turner Syndrome (45 X, null): short stature, primary amenorrhea, web neck, poor breast development, coarctation of aorta
* Tx: estrogen
* Delayed growth: undernutrition, chronic disease
* Attenuated growth: malnutrition, severe chronic diseases, GI disease, metabolic/endocrine disease (hypothyroidism, Cushing’s)
* Constitutional delay of growth (late bloomer): normal growth velocity, delayed skeletal maturity, delayed puberty, normal final height
49
Provide etiologies of tall stature divided between childhood and adult
* Tall stature
* Childhood (normal adult height)
* Exogenous obesity, precocious puberty, hyperthyroidism
* Adult
* Familial tall stature, excess GH secretion, androgen/estrogen deficiency, Klinefelter syndrome (XXY), XYY, Marfan syndrome
50
For the following diseases provide the trend of the height velocity, weight gain, and any other info:
* Undernutrition
* Hypothyroidism
* Growth hormone deficiency
* Cushing's
* Turner Syndrome
* Overnutrition
* Klienfelter
51
Define puberty and provide 4 different events in females and males that occur.
* Puberty: transition from childhood to sexual maturity
* General physiologic events:
* Gonadarche: activation of gonads by GnRH → LH/FSH
* Adrenarche: increase in androgen synthesis by adrenal cortex → stimulates hair, acne, and body odor
* Spermarche: first sperm production
* Pubarche: appearance of pubic hair
52
What is the general puberty timing in males and females?
Provide the order of devleopment of different organs.
* Puberty timing (can change based on ethnicity)
* Male: onset is 9-14 y/o
* Gonadarche (testicular growth) → adrenarche → phallic growth → growth spurt (later than females)
* Female: onset is 8-13 y/o
* Thelarche (breast development) → adrenarche → growth spurt → menarche
53
How is GnRH released in pre-puberty when compared to puberty.
How are the pre-puberty release of GnRH activated and inhbitied?
What are physiological changes during puberty in hormones?
* Pre-puberty: low and infrequent GnRH pulses
* Suppression due to: GABA, MKRN3
* Activation due to: glutamate, leptin, kisspeptin, neurokinin B
* Puberty: increased frequency of GnRH pulses
* Physiological changes: development of zona reticularis of adrenal glands → increase in DHEAS, androstenedione, and testosterone
54
What are pubertal changes associated with estrogen in a female?
Explain the associated tanner changes here.
* Estrogen → growth spurt, body weight composition, bone growth, genital maturity, and breast development
* Tanner Stages for breast
* I (pre-pubertal): no breast tissue or changes
* II-IV (pubertal changes): breast bud starts to develop and areola starts to separate from the nipple
* V (mature stage): fully developed
55
What are pubertal changes associated with androgens in a female?
Explain the associated tanner changes here.
* Androgens → pubic hair
* Tanner Stages for pubic hair (true for males as well)
* I (pre-pubertal): no hair
* II-IV (pubertal changes): transformation from minimal hair to hair all around genitalia
* V (adult appearance): hair from thigh to thigh
56
What are pubertal changes associated with testosterone in a male?
Explain the associated tanner changes here.
* Male
* Testosterone → growth spurt, testicular size, spermarche, and genitalia development
* Tanner stages for genitalia
* I – prepubertal
* II – enlargement of testes and scrotum, scrotal skin reddens/texture change
* III – penis enlarges (length 1st), testes grow
* IV – increase in width, development of glans, testes & scrotum larger, scrotal skin darker
* V – adult genitalia
57
Define precocious puberty and the age
* Precocious puberty: early sexual maturation (\< 9 y/o for boys, \< 8 y/o for girls)
58
How does central precocious puberty work and how is it treated?
* Central: GnRH-dependent sex hormone production → FSH/LH secretion is normal → results in iso-sexual sequential maturation (females → females)
* Treatment: decide if needed
59
How does peripheral precocious puberty work? Give some etiologies. Give overall tx
* Peripheral: GnRH-independent sex hormone production → FSH/LH suppressed → results in iso-sexual or contrasexual (male develops as female) maturation
* Etiology: Genetic (CAH, LH-R activating mutations, DAX1 gene mutations, McCune Albright syndrome) and tumors (adrenal, pituitary, ovarian, testicular)
* Treatment: treat underlying disorders
60
What is McCune Albright syndrome? What signs are associated with it?
What does it cause?
* McCune Albright syndrome: precocious puberty due to recurrent ovarian cysts and intermittent estrogen secretion
* Signs: Café-au-lait skin lesions (coffee w/milk color), polyostotic fibrous dysplasia (lytic lesions in the bones)
* CAUSES PERIPHERAL PRECOCIOUS PUBERTY
61
For benign premature thelarche, provide:
* description
* etiology
* red flags
* diagnosis
* Benign premature thelarche
* Description: unilateral or bilateral breast development before the age of 2 with no other signs of puberty → regresses by age 2-3 y/o
* Etiology: environmental
* Red flags: lack of regression by age 3, breast d/c, other signs of puberty
* Diagnosis: bone age, LH/FSH, estradiol, imaging (head)
62
What are the ages for delayed puberty in each gender?
* Delayed puberty (\>13 y/o for girls, \>14 y/o for males)
63
What are examples of the following:
* Constitutional
* Delayed, but spontaneous
* Constitutional delay (majority, especially in males)
* Delayed, but spontaneous (functional hypogonadotropic hypogonadism)
* Due to chronic disease, but normal HPG axis
* Examples: Inflammatory disease, malnutrition, exercise, hypothyroidism, prolactinoma, craniopharyngioma
64
What are examples of the following:
* Hypogonadotropic hypogonadism (one syndrome, provide pathophys, sx and tx)
* Hypogonadotropic hypogonadism
* Ex: Kallmann syndrome – GnRH containing neurons failed to migrate from the olfactory placode to hypothalamus → lack of hormonal stimulation → no puberty
* Symptoms: anosmia (dx: test olfaction)
* Treatment: exogenous hormones
65
For hypergonadotropic hypogonadism, provide description, labs, and etiology
* Hypergonadotropic hypogonadism
* Description: results of gonadal failure, intact HPG axis
* Labs: elevated FSH
* Etiology: Turner syndrome, Klinefelter syndrome, irradiation, chemotherapy, infection (dx: karyotype)
66
Provide two examples of unclassified delayed puberty
* Unclassified (anatomical abnormalities)
* Mullerian agenesis (Mayer-Rokitansku-Küster-Hauser syndrome (MRKH)
* Most common cause of primary amenorrhea because of absence of vagina, uterus and fallopian tubes; ovarian function is normal
* Imperforate hymen, transeverse vaginal septum
67
Situations for elective and medically induced abortions?
* Elective: unintended pregnancy, domestic issues
* Medically-indicated: risk to mother’s life, ectopic pregnancy
68
Two meds for medication induced abortion? Provide MOA and SE if any?
When are these indicated?
* Medication-induced abortion (indicated up to 70 days with ~70% success)
* Prostaglandin E1 analog – Misoprostol (given at very high dose on day 2)
* MOA: cervical ripening and uterine contractions
* SE: severe cramping, heavy bleeding
* Antiprogesterone – Mifepristone (given day 1)
* MOA: lack of progesterone à lack of uterine maintenance à abortion
69
Provide surgical methods to abort a baby? Provide MOA and inidcations.
When is a baby viable?
* Surgery (indicated after 70 days to end of first trimester)
* MOA: suction, dilation, and evacuation à abortion
* Viability starts ~24 weeks, so many states will not abort during the second trimester onwards
70
What are the provider roles in abortion?
* Understand that it is the patient’s decision and that it is difficult concept
* You must manage complications (death of mother), review obstetric history, and manage psychological impact of the abortion on the patient
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