Gonadal Hormones: Progesterone and Estrogen Flashcards
Explain the hormonal regulation of hypothalamic pituitary axis
Increased TRH — increased TSH (pituitary hormone) — increased T3 and T4 (pituitary hormonal effect)
Increased GnRH — Increased FSH and LH —– Increased Estrogens, Progesterone and Testosterone
Increased CRH —- Increased ACTH, MSH, and Beta-Endorphins —- Increased Mineralocorticoids, Increased Glucocorticoids and Sex Hormones (DHEA)
Increased GHRH — Increased GH — Increased IGF-1
Explain the various stimulation (prolactin, exercise, glucose and dopamine) on hormone secretion
Increased Prolactin —– Decreased GnRH — Decreased Spermatogenesis and Ovulation
Increased Exercise and Sleep — Increased GHRH — Increased IGF-1
Decreased Glucose and Somatostatin — Increased GHRH —Increased IGF-1
Increased Dopamine (dopamingeric drugs) — Decreased prolactin — Increased GnRH
What are the major categories of natural sex steroids?
- Estradiol (Estrogens)
- Progesterone
- Androgens
What is the general mechanism of action of steroid hormones (estrogen, progesterone and testosterone)?
- Binds to the cytosolic receptor
- Hormone receptor complex (HRC) travels into nucleus
- Activation of HRC leads to changes in the rates of transcription of steroid hormone regulated genes this modulates gene expression
Know the picture on slide 13 of 62
Glomerulosa: Mineralocorticoids (Aldosterone)
Fasciculata: Glucocorticoids (Cortisol)
Reticularis: Androgens (DHT and testosterone)
If a patient has 17 alpha hydroxylase deficiency this leads to what?
Decreased sex hormones and cortisol
Increased mineralocorticoids (aldosterone)
–pathway is on slide 14
How will a patient present with 17 alpha hydroxylase deficiency?
Increased BP and decreased Potassium
If XY: decreased DHT show cryptochidism and indistinct genitalia (tx with androgens, glucocorticoids, and HTN meds)
If XX: outwardly phenotypic female with normal internal sex organs but lack of secondary characteristics (tx with estrogens and HTN meds)
If a patient has 21 hydroxylase deficiency this leads to what?
Increased sex hormones
Decreased cortisol and mineralcorticoids (aldosterone)
How will a patient present with 21 hydroxylase deficiency?
Decreased BP but Increased Potassium and Increased Renin activity and volume depletion
If XY: over masculinization
If XX: pseudohermaphroditism
Rx: fluids + salt repletion and administer cortisol to decrease ACTH
If a patient has 11 beta hydroxylase deficiency this leads to what?
Increase in sex hormones
Decrease in cortisol and in mineralocorticoid (Aldosterone)
Increase in 11- deoxycorticosterone
How will a patient present with 11 beta hydroxylase deficiency?
Increased BP due to increased mineralocorticoid 11- deoxycorticosterone
Over masculinization
Rx: estrogens and Anti-HTN
What are some features of estrogen?
Sources: Ovary, adrenal gland, placenta and in adipose tissue via aromatization
Main estrogens: Estradiol (more potent), Estrone, Estriol
Estriol is for pregnancy
In regards to drugs, what are the various antiestrogens?
Receptor antagonist: selective estrogen receptor modulators and Full antagonist (Fulvestrant) Aromatase inhibitors GnRH Agonist (continuous administration)
What are the physiological effects of estrogen?
Sexual development: growth and development of vagina, uterus, fallopian tube, breast enlargement
Non-reproductive functions: reduce bone resorption and prevent bone loss and epiphyseal closure in long bones
Pro-coagulation state: increase factor II, VII, IX, X, XII in higher doses and decrease in antithrombin III, protein C and S
Favorable lipid profile: increase HDL and decrease LDL
Effect on Hormone levels: increase the transport protein level of various hormones and free hormone level is unaffected
Increased cholesterol in bile: formation of gall stones
What are the estrogen drugs?
Ethinyl Estradiol Conjugated Estrogen Mestranol Diethylstilbestrol Estradiol Estrone Estriol
What is Mestranol?
Prodrug converted into Ethinyl Estradiol, present in some contraceptives
–increased bio-availability, increased half life and decreased FSH and LH via feedback
Metabolism of estrogens relies on cytochrome P-450 system; they have enterohepatic circulation. There combination with P-450 inducers leads to what?
Failure of contraceptive effectiveness
What are the clinical uses of Estrogens?
IM: long acting estrogen preparations are used in females with hypogonadism
Oral contraceptives in combo with progestins: suppress FSH and LH secretion and inhibit ovulation
Postmenopausal hormone replacement therapy (HRT): help and reduce hot flashes, prevent bone loss and fractures, decrease incidence of colon cancer, decrease urogenital atrophy and increase feeling of well being
Used in dysmenorrhea, uterine bleeding, prostate cancer, and acne
What are benefits associated with estrogen replacement therapy?
Osteoporosis: estrogen decreases the resorption of bone but has no effect on bone formation. decreases the frequency of hip fractures. tx with estrogen must begin right after menopause
Vasomotor: estrogen treatment reestablishes feedback on hypothalamic control of NE secretion, leading to decreased frequency of hot flashes
Urogenital Tract: Estrogen treatment reveres postmenopausal atrophy of the vulva, vagina, urethra, and trigone of the bladder
What are the adverse effects of estrogens?
- increased incidence of thromboembolism
- Increased incidence of breast cancer
- Endometrial hyperplasia and cancers
- Migraine, cholestasis, and mood changes
- Nausea, breast tenderness and bloating
- Diethylstilbestrol (DES): a non-steroidal estrogen agonist use in pregnancy results in female child to infertility and vaginal cancer
What are contraindications for estrogen use?
- History of thromboembolism
- Breast and Endometrial Cancer
- Pregnancy
- Liver Disease
Selective Estrogen Receptors Modulators (SERMs): exhibit agonistic action in some tissues and antagonists in other tissues. Explain this using Tamoxifen
Tamoxifen: E-receptor antagonist effect on breast tissue but agonist effect on liver, bone and partial agonist endometrium
- -used in tx of breast cancer and prophylaxis for high risk patients
- -AE: hot flushes (antagonist) and thrombosis (agonistic) and risk of endometrial cancers
The next two SERMs are Toremifene and Raloxifene what are some features?
Toremifene: tx of breast cancer and prevention of breast cancer in high risk women
Raloxifene: E- receptor antagonist at breast but agonist at bone (increase in bone density). No estrogenic effect on endometrium – so no increased risk of endometrial cancer. Use: prophylaxis against breast cancers and prevention of postmenopausal osteoporosis
What is the estrogen receptor antagonist in all tissues?
Fulvestrant IM: used in tx of breast cancer in tamoxifen resistant patients
AE: hot flushes, injection site reactions and headache
