Reproductive Endcrinology Flashcards
Hypothalamic-Pituitary-Gonadal Axis
Hypothalamus: Makes GnRH
Pituitary: Makes LH & FSH
Gonads: Make Androgens, Progesterones, Testosterones, Estrogens, etc.
Endocrine Cells of the Testes
- Leydig cells – secrete testosterone and other androgens, estrogens and progestins
- Sertoli cells – spermatogenesis
- secrete inhibin
- form tight junctions to create a “blood-testis” barrier
Seminal Fluid/Ejaculate Composition
- Composition comes mostly from where?
- 60% Seminal vesicles: fructose, phosphorylcholine, ascorbic acid, prostaglandins
- 20% testes: Sperm
- 20% prostate
Semen analysis & parameters
- Three or more samples obtained by masturbation
after 48 hours of abstinence
Parameters:
- Concentration
- Motility
- Morphology
If abnormal sperm analysis, what is the first test you run?
Measure:
- Testosterone
- LH
- FSH
Primary testicular failure: High LH & FSH, but low T
Hypogonadotrophic Hypogonadism: Low LH, FSH and T
What 2 hormones are derived from testosterone?
- Dihydrotestosterone
2. Estradiol
What enzyme converts Testosterone to DHT?
5-alpha-reductase
Roles of DHT
- Greater affinity for androgen receptor than T (more potent androgen)
- In embryogenesis, formation of male external genitalia (low DHT can cause ambiguous genitalia)
- Male pattern hair loss (alopecia)
- Benign prostatic hypertrophy
- Prostate cancer
Proteins that bind circulating testosterone
Sex Hormone Binding Globulin (SHBG): tight binding (not bioavailable, but included in total testosterone measurement)
Albumin: weak binding (testosterone is bioavailable)
Testosterone Measurement
- Variable throughout the day b/c of pulsatile LH release
- Highest levels of testosterone in the morning
- Multiple measurements recommended
- Free Testosterone decreases with age b/c of increased production of SHBG
Signs & Symptoms of Low Testosterone
Common:
- decreased libido
- erectile dysfunction
- regression of secondary sex characteristics
Other:
- osteoporosis
- decreased muscle strength
- depression, lethargy, inability to concentrate, sleep disturbance, irritability, decreased interest in activities
- incomplete sexual development
- breast discomfort, gynecomastia
- very small or shrinking testes (< 5 ml)
- infertility
- mild anemia
- decreaed spontaneous erections
- hot flushes, sweats
Causes of Primary Hypogonadism in Males
**What test should your perform if suspect primary hypogonadism?
- Klinefelter’s Syndrome
- Mumps orchitis
- Testicular trauma (bicycle accident)
- Radiation
- Autoimmune disease
- Drugs (cyclophosphamide, chemotherapy)
** If low T with high LH/FSH: KARYOTYPE
Characteristics of Klinefelter’s Syndrome
Karyotype: XXY
- Sparse facial & body hair
- Gynecomastia
- Small, firm testes: seminiferous tubules undergo fibrosis and hyalinization
- Female body habitus
Causes of Secondary Hypogonadism in Males
**What test should your perform if suspect secondary hypogonadism?
- Pituitary disorders:
tumor, trauma, infiltrative
hemochromatosis (iron deposition)
hyperprolactinemia
hypopituitarism - Hypothalamic tumor/trauma
- Critical illness: ** if acute or subacute, do not make diagnosis of androgen deficiency
- Congenital disorders of gonadotropin secretion (i.e. Kallmann’s Syndrome with anosmia)
- Drugs (marijuana, heroin, opiates, progesterone)
** if low T, LH/FSH: measure PROLACTIN
Adverse Effects of Testosterone Therapy
- Erythrocytosis: Increase in RBC mass
- up to 44% with IM injections - Skin reactions: high incidence with patch; low incidence with gel
- Acne (rare)
Gynecomastia (definition & mech)
- Enlargement of glandular breast tissue
Mechanism: imbalance between free androgen and estrogen in breast tissue
- Can have either low androgen, or too much estrogen
Pseudogynecomastia
Subareolar fat
Aromatase
Enzyme that converts testosterone to estradiol
Hypothalamic Regulation & GnRH
- GnRH is released in a pulsatile manner
- varies throughout menstrual cycle
- estradiol (low), norepinephrine: increase GnRH release
- progesterone, dopamine, opioids, serotonin: decrease GnRH release
GnRH agonists (continuous GnRH release) suppresses reproductive axis. You want want to do this for:
- precocious (early) puberty
- endometriosis (ectopic endometrial tissue)
- prostate cancer – androgen blockade
Clomiphene – antiestrogen; removes negative feedback
- Ovulation induction by ↑ FSH and LH
Polycystic Ovarian Syndrome
- classic presentation?
- treatment?
Presentation:
- Obese young woman
- Infertility
- Oligomenorrhea
- Hirsutism
- May develop Type 2 Diabetes Mellitus
Characterized by increased LH, but low FSH
** increased frequency of GnRH pulses favors LH > FSH
Definition: At least 2 out of 3: (diagnosis of exclusion)
- amenorrhea or oligomenorrhea (<9 menses/year)
- hyperandrogenemia (high testosterone levels) or clinical hyperandrogenism (hirsutism, acne, male-pattern hair loss)
- polycystic ovaries on ultrasound
Treatment:
- start with weight loss
Match Condition with Lab Test:
- Hyperprolactinemia
- Non-classical congenital adrenal hyperplasia
- Cushing’s
- Androgen secreting tumor
- Acromegaly
Lab Test:
- Prolactin
- 8 am 17-OH Progesterone
- 24 hour urine of free cortisol
- Testosterone, DHEA-S
- IGF-1
Primary Amenhorrhea
- Definition
- Causes
Definition: Lack of menses by age 16
- Pregnancy: ✓ Serum hcg
- Turner’s Syndrome ✓ Karyotype (XO)
- Ovarian Failure ✓ High FSH
- Hyperprolactinemia ✓ Prolactin
- Hypothyroidism ✓ TSH
Turner’s Syndrome
Physical:
- Streak–like gonads
- short stature
- webbed neck
- shield chest
- low set ears
- ptosis
- short 4th metatarsals/carpals
Karyotype: XO or mosaic
Treatment
- Estrogen at age 12-13
- Progesterone added at age 14
- Growth hormone (increased height)
Congenital Adrenal Hyperplasia
- Due to enzymatic deficiency of 21-Hydroxylase
- 21-Hydroxylase is required for conversion of:
1. Progesterone to Mineralocorticoids (Aldosterone)
2. 17-OH Progesterone to Glucocorticoids (Cortisol)
Clinical:
- Ambiguous Genitalia: b/c Hormone production is shunted to the sex hormones
- “Salt losers”: insufficient aldosterone
- hyponatremia (Na+)
- hyperkalemia (K+)
- acidosis
- dehydration
- vascular collapse - Impaired cortisol biosynthesis
Hirsuitism
- definition
- cause
- labs
- Excessive terminal hair in a male pattern on a woman (abdomen, back, chest)
- results from the interaction between androgens and the hair follicles w/ increased androgen sensitivity
Labs:
- no labs for idiopathic: mild, w/ regular menses
- FREE TESTOSTERONE is the best initial lab (because androgens and insulin lower SHBG, such that the total testosterone may be normal)
Hypertrichosis
- generalized excessive hair growth in a non-sexual pattern due to hereditary or medications (glucocorticoids, phenytoins, minoxidil or cyclosporine)
- not caused by excessive androgen
Endocrine Treatment for Transexual Females
- i.e., Male to Female
TREATMENT
- Estradiol valerate (transdermal E2 less thrombogenic)
± Antiandrogens (spironolactone, cyproterone acetate)
± Medroxyprogesterone acetate 5-10 mg/d
LAB MONITORING
- Testosterone
- Estradiol
- Lipids and LFTs
- Prolactin
SCREENING
± PSA
- DXA bone density
- consider mammogram (breast cancer 1 in 2200)
Endocrine Treatment for Transexual Males
- i.e., Female to Male
TREATMENT
- Testosterone esters 200 mg IM q 2 weeks
- Transdermal testosterone 5 g/day ± progesterone
LAB MONITORING
- Testosterone
- Lipids
- LFTs
- Glucose
- Hematocrit
SCREENING
- Pelvic exam with Pap smears
- Endometrial ultrasounds
- DXA bone density
Legitimate uses of Anabolic Androgenic Steroids
- Osteoporosis: ↑ bone mineral density
- Hematopoietic:
- Anemia of end-stage renal disease (ESRD); erythropoietin dependent and independent
- Aplastic anemia
- Fanconi anemia - Growth: Constitutional delay of growth and puberty
- Muscle wasting disorders: AIDS and cancer
How AAS can improve athletic performance
1. Muscle Hypertrophy: ↑ muscle fiber diameter ↑ lean body mass - Positive nitrogen balance - Retention of potassium, phosphates and sulfates
- Blood Volume: ↑ red cell mass
- Glucocorticoid Receptor Antagonists: Inhibit catabolism
- Central Nervous System: Function of androgen receptors in the brain is unclear
Physiological/Hormonal Effects of AAS
- Testosterone increased
- SHBG: dereased
- Estradiol: increased
- LH & FSH: shut down
- Hematocrit: slight increase
Liver Function Tests:
- ALT: increased
- AST: increased
Lipids:
- HDL: decreased
Adverse effects of AAS
- Acne
- Oily skin
- Infertility
- Liver toxicity
- Mood swings & cognitive impairment
Women:
- Anovulation
- Amenorrhea
Men:
- Testicular atrophy
- Gynecomastia
Serious but rare:
- Hepatocellular adenoma and carcinoma
- Peliosis Hepatis: blood-filled cysts in liver or spleen
- High doses can induce mania or severe depression
Detecting AAS in Urine Samples
- use chromatograph or mass spectrum of substance
- measure Testosterone:Epitestosterone (T:E) Ratio (Normal is 1:1; elevated to 8:1 after injection)
