Pharm Final: Gonadotropins

  1. What are the 4 hormones excreted from the ovary?
    • 1. Estrodiol
    • 2. Progesterone
    • 3. Testosterone
    • 4. Inhibit
  2. What are the 3 hormones excreted from the testicles?
    • 1. Testosterone
    • 2. Androgen binding protein
    • 3. Inhibin
  3. GnRH is affected by which 3 hormones NT and do they inhibit or stimulate?
    • 1. Dopamine--> (-) inhibits
    • 2. Endorphins--> (-) inhibits
    • 3. NE--> (+) stimulates
  4. Of the 2 estrogen receptors ER-a & ER-b, which is a negative feedback?
    Negative feedback--> ER-a
  5. Fast pulse of GnRH released from the hypothalamus produces FSH or LH? Slow pulses?
    • Fast pulses--> LH
    • Slow pulses--> FSH
  6. Low levels of estrogen stimulate or inhibit FSH?
    • Low levels E2--> stim FSH
    • High levels E2--> inhibit FSH
  7. Low levels of progesterone stim or inhibit FSH?
    Low levels Pg--> STIM FSH
  8. What are the 3 effects of FSH on the follicle?
    • 1. Stimulate granulosa cells to release E2
    • 2. Aromatizes androgens to E2
    • 3. Induces LH receptors on theca cell
  9. What is the effect of LH?
    1. Stimulates ovulation (switches cells to Pg production)
  10. What does the LH surge do?
    • 1. Luteinizes theca & granulosa cells (produce Pg)
    • 2. Inhibit further cell growth
    • 3. Drives oocyte into 1st meiotic division
    • 4. Weakens wall of follicle
  11. What are 3 disruptions to the cycle?
    • 1. Stress
    • 2. Weight loss
    • 3. Pituitary adenomas
  12. What are the 3 types of estrogen and where are they excreted?
    • 1. E2--> ovaries
    • 2. E1--> fat
    • 3. E3--> placenta
  13. Where is a majority of estrogen excreted?
  14. What are the adverse SE of synthetic E2 1st pass effect in liver?
    • -Increased clotting factors
    • -Increased plasma renin substrate
  15. What is the MOA of synthetic estrogen?
    • -Disassociates from SHBG--> binds to ERa or ERb--> changes conformation--> releases HSP
    • -Binds to estrogen response elements--> often a promotor gene
  16. Where is ERa mainly expressed? ERb?
    • ERa--> uterus, liver, kidney, and heart
    • ERb--> ovary, prostate, lung, GI, bladder, heme, CNS

    Both--> mammary, epididymis, thyroid, adrenal, bone, some brain
  17. What are 4 generalized effects of estrogen?
    • 1. Female maturation
    • 2. endometrial regulation
    • 3. Metabolic/cardio effects
    • 4. coagulation
    • 5. Others: Pg receptor synthesis, libido, SNS well-being, fluid shifts (bloating)
  18. What are the uses of Estrogen?
    • 1. Primary hypogonadism
    • 2. Postmenopausal HRT
    • 3. Others: Hemorrage (ob)
    • 4. Ovulation suppression
  19. What are the benefits and risk of E2 only?
    • B: ⇓ hot flashes, osteoporosis, Br Ca
    • R: ⇑Blood clots, stroke, CAD
  20. What are the risk/benefits of E2 + Pg?
    • B: ⇓ Hot flashes, osteo, colorectal cancer
    • R: ⇑ Blood clots, stroke, CAD, Br. Ca
  21. What is the difference in risk fo E2 only and E+P?
    E+P has increase risk for Breast Cancer
  22. What is the difference in benefit between E2 only and E + Pg?
    E+P has added benefit if decreased colorectal cancer risk
  23. What are some random other uses of Estrogen?
    • Breast cancer
    • prostate cancer
    • wound healing
    • Growth in girls
    • Bulimia
    • Trauma liver injury
  24. Where is the primary source of progesterone synthesis?
    • Ovary (CL)
    • --> also in testis, adrenal gland, and placenta
  25. How is progesterone excreted?
    Renally (almost complete 1st pass in liver)
  26. MOA: progesterone
    • -Ligand-receptor complex--> activate gene transcription
    • -Depends on receptor coregulators
    • -some splicing
  27. T or F. Progestin has little impact on protein?
    True--> favors fat deposition
  28. What are the effects of progestin on carbs?
    • -Increase basal insulin
    • -Increase insulin response to glucose
    • -Promote glycogen storage
    • -promotes ketogenesis
  29. T or F. Progestin competes w/ aldosterone & mineralocorticoid receptors.
    True--> ⇓ NA reabsorption--> increase aldosterone secretion
  30. T or F. Synthetic progestins don't alter respiratory function.
    True--> natural do
  31. What is the effect of progestin on the endometrium?
    -maturation and secretion
  32. What are the therapeutic uses of Pg?
    • 1. hormone replacement
    • 2. Contraception
    • 3. Pregancy/infertility
  33. What are 3 contraindication of Pg?
    • 1. Increase BP in women
    • 2. Androgenic synthetic Pg--> decrease HDL
    • 3. Postmenopause--> Increase Br Ca risk
  34. Inhibit increases or decreases FSH secretion?
    Decreases FSH
  35. Activin increases or decreases FSH secretion?
  36. What is the action of Activin with FSH? Activin with LH?
    Activin w/ FSH--> stimulates granulosa cells to synthesize Pg & aromotase

    -Activin w/ LH--> ⇓ Pg, but markedly increases aromatase
  37. Discuss relaxin?
    • -Synthesized by luteinized granulosa cells
    • -Found in ovary, placenta, uterus, & blood
    • -Insulin-like--> increase glycogen, H20 reuptake in myometrium, decrease uterine contractility
    • -Clinical trials--> dysmenorrhea, premature labor
  38. What are the 2 Progestin families?
    • 1. Estrane
    • 2. Gonane
  39. MOA: Progestin
    Selective inhibition of pituitary
  40. T or F. Progestin only may NOT inhibit ovulation.
  41. What are the 3 physical effects of combined E+P?
    • 1. Mimics pregnancy--> inhibits ovulation
    • 2. Alters cervical mucous
    • 3. Alters tubal motility
  42. T or F. Progestin only alters tubal motility?
    False (E+P does)
  43. What is the effect of progesterone on the uterus?
    Atrophic endometrium (unless E added)
  44. What is the effect of progestin on the binding globulins in the body?
    Increased! (TBG, CBG, SHBG)
  45. What are the effect of progestin on lipids?
    -Increase TG and HDL
  46. T or F. Pg causes increased insulin resistance.
    True (and decreased carb absorbed from gut)
  47. What is the effect of progestin on the RAAS?
    -Increase plasma renin--> increase aldosterone
  48. What is the effect of Pg on the cardio system?
    -Increased BP, HR (may be profound in some women)
  49. What are "mild" adverse side effects of Pg?
    • -Nausea, mastalgia, BTB, edema (E effects)
    • -H/A, worsening migraines
    • -amenorrhea
  50. What are some "moderate" effects of Pg (+E)?
    • -BTB only in Pg
    • -Wg gain (depo)
    • -pigmentation (cholasma, linea nigra)
    • -Bacturia (ureteral dilation)
  51. Severe Adverse SE of Pg (+E).
    • -Thromboembolism (VTE, MI, CVA)
    • -GI: jaundice, gallbladder
    • -Depression
    • -Cancer (reduced ovarian/endo)
  52. Contradindations for OCPs?
    • -Thrombophlebitis, coagulopathy
    • -Cardio issues
    • -Unexplained vag bleeding
    • -Pregnancy
    • -cancer (e-dependent)
    • -Avoid: liver dx, asthma, eczema, migraine, DM, HTN, optic/retrobulbar neuritis, seizure d/o
  53. What drug is a competitive partial agonist inhibitor working at the Estrogen receptor?
    Tamoxifen (SERM)
  54. Which drug is a partial E2 agonist?
    Clomiphene (clomid)
  55. Which is the effect of clomid?
    inhibits negative feedback--> increasing FSH (good to improve ovulation)
  56. What are the adverse effects of clomid?
    • -Hot flashes
    • -H/A, constipation, allergic skin rxn
    • -Increase endometrial implant growth
    • -N/V, depression, fatigue, breast tenderness, wt gain
    • -Mult gestation
  57. What is the MOA of Mifepristone?
    Binds tightly to Pg receptor (inhibiting Pg activity)
  58. What are the uses of Mifepristone?
    • -Misoprostol--> abortifactant
    • -Experimental--> endometriosis, cushings, Br Ca
  59. What are the adverse effects of Mifepristone (Pg inhibitor)?
    • -V/D, abdominal/pelvic pain
    • -heavy bleeding
  60. MOA: Danazol
    -Binds to androgens, progesterone & glucocorticoid receptors
  61. What are the effects of Danazol?
    • -Suppress ovarian function (inhibit LH surge)
    • -Inhibit gonadal function
  62. What is Danazol used for?
    • -Endometriosis
    • -Breast pain, hemophilia, Xmas Dx, ITP, angioneurotic edema
  63. What are adverse effects of Danazol?
    1. Wt gain, edema, decrease breast size, acne, increased hair growth, deepening voice, H/A, hot flashes, libido changes, muscle cramps, adrenal suppression
  64. What is the effect of Aromatase Inhibitors? When is it used?
    • -Inhibits estrogen synthesis
    • -Uses in Breast Cancer
  65. What weak estrogens are produced in the testis?
    • 1. Androstenedione
    • 2. DHEA

    **majority secreted from adrenal glands
  66. Discuss Androstenedione, DHEA, DHEAS
    • -Produced in adrenal gland
    • -Important for "well-being"
    • -⇑ SHBG binding w/ ⇑ E, thyroid hormone, cirrhosis
    • -⇓ SHBG binding w/ ⇑ androgen, GH, obesity
    • -33% bound to albumin
  67. What substance converts Androgen to dihydrotestosterone?
  68. What substance converts Androgens to Estrodiol?
    Aromatase (fat, liver, hypothalamus regulation)
  69. What are 5 effects of androgens?
    • 1. Growth (ht, wt, lean m. mass)
    • 2. Genital (growth, prostate, seminal vesicle)
    • 3. Skin (puberty hair, sebaceous glands, darkening of skin
    • 4. Larynx & vocal cords thicken
    • 5. Sexual function
  70. What are the uses of synthetic androgens?
    • 1. anabolic effects
    • 2. hormone replacement
  71. When is androgen replacement used?
    • -Hypopituitarism (gradually increase dose for growth spurt & 2nd sexual characteristics
    • **only use GnRH if spermatogensis is goal
  72. Adverse effects of Androgens?
    • -Women: masculinization, progestational activity, endometrial bleeding, atherosclerotic dx
    • -Infants--> over/under masculinzation of genitalia
    • -Men--> acne, sleep apnea, erythrocytosis, gynecomastia, azoospermia
    • -Everyone--> Na+ retention/edema, hepatic dysfunction
  73. What are cautions/contraindications of Androgen replacement?
    • -NOT in pregnancy
    • -Prostate/Breast Ca
    • -young children
    • -Renal/cardiac disease
    • -Hepatocellular ca
  74. When is androgen suppression use?
    • -Advanced Prostate cancer
    • -Androgen overproduction (use steriod synthesis inhibitor like ketoconazole)
  75. What are 3 ways to suppress androgen and a drug example of each?
    • 1. Steroid synthesis inhibitors (ketoconazole)
    • 2. Halt steroid conversion (Finasteride)
    • 3. Receptor inhibitors (Flutamide & spironolactone)
Card Set
Pharm Final: Gonadotropins