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6. HDS GI Repro > Therapeutic Sex Hormone > Flashcards

Therapeutic Sex Hormone Flashcards

1
Q

Reproductive Hormones

Biosynthesis

A
  • Cholesterol → pregnenolone → progesterone
  • Can lead to production of 5 classes of steroids: estrogens, androgens, progestins, mineralocorticoid, glucocorticoid
  • Progesterone produced 1° by the ovary, corpus luteum, and placenta
    • Helps maintain pregnancy
  • In ♀, estrogen produced by ovaries (follicle and corpus luteum) &
  • *fetal-placenta unit**
    • Estradiol = most potent estrogen analogue
    • Estrone and similar molecules generated peripherally via conversion of precursor androstenedione
      • 1° mech. for estrogen synthesis in postmenopausal women
      • 1° in adipose tissue
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2
Q

Reproductive Hormones

MOA

A
  • Estrogens, progestins, and testosterone ⇒ specific nuclear receptors in cytosol
  • Hormone-receptor complex (dimer) ⇒ specific response elements on DNA ⇒ ∆ transcription
    • Estrogen response element = ERE
  • Expression of coactivators and corepressors ⇒ another level of regulation
    • Varies from tissue to tissue
  • Binding of a selective estrogen receptor modifier (SERM) ⇒ ∆ conformation of estrogen receptor ⇒ allows binding of coactivator or corepressor
    • Recruitment is tissue specific
    • SERM’s can be antagonists in some tissues and agonists in other tissues
    • Tamoxifen is an example of this
  • Many effects of testosterone mediated by dihydrotestosterone
    • Conversion via 5-α-reductase
  • Separate receptors exist for all the steroid hormones
  • Synthetic progesterone analogues can activate testosterone receptors ⇒ androgenic effects
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3
Q

Hypothalamic-Pituitary-Ovary Axis

A
  • Input via environmental cues → hypothalamus
    • Transforms neural signals → neuropeptide output (GnRH)
  • GnRH ⇒ ⊕ ant. pituitary ⇒ gonadotropins ⇒ ⊕ steroid hormone production & gamete development in ovaries and testis
  • Follicular stimulating hormone (FSH) ⇒ ⊕ ovarian follicle development & estrogen synthesis in ♀ / ⊕ spermatogenesis in ♂
  • Luteinizing hormone (LH) ⇒ ⊕ ovulation & luteinization in ♀ / ⊕ androgen synthesis in ♂
  • Ovarian steroid hormones:
    • Prepares endometrial lining for pregnancy
    • Feedback to hypothalamus and pituitary to regulate gonadotropins
    • Many of steroid hormones synthesized locally, where they exert many of their physiological effects
    • Circulating estrogen administered pharmacologically ⊗ FSH/LH secretion ⇒ ↓ local production of estrogen
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4
Q

Menstrual Cycle

Endocrine Control

A
  • Start of menstrual cycle: low estrogen ⇒ ↑ FSH and LH secretion ⇒ maturation of several follicles
  • Maturing follicles ⇒ estrogen ⇒ ↑ LH and FSH receptors ⇒ ↑ estrogen secretion
  • One follicle supersedes others in estrogen secretion and responsiveness to LH and FSH
    • ↑ Estrogen levels ⇒ ⊗ LH and FSH secretion ⇒ other follicles become atretic
    • Estrogen causes proliferation of endometrial lining
  • Brief ↑ in estrogen levels ⇒ ⊕ feedback of gonadotropin release ⇒ LH surge ⇒ ovulation
  • Ruptured follicle → corpus luteum ⇒ estrogen and progesterone
    • Progesterone ⇒ endometrial lining switches to secretory state
  • Corpus luteum life span ~ 14 days
    • No fertilization ⇒ atresia
  • Fertilization ⇒ implantation ⇒ blastocyst ⇒ human chorionic gonadotropin (hCG)
    • hCG ⇒ ⊕ corpus luteum to continue to secrete progesterone ⇒ helps maintain pregnancy
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5
Q

Estrogen

Preparations

A
  • Conjugated equine estrogens (CEE)
    • Premarin and Prempro
    • Isolated from urine of pregnant mares
    • Used for HRT
  • Synthetic estrogen
    • Ethinylestradiol
      • Used in oral contraceptives
      • ∆ 17 position ⇒ orally active
    • Mestranol is a less commonly used prodrug for ethinylestradiol
  • Transdermal estradiol
    • Used for HRT or contraception
  • Estradiol cypionate and estradiol valerate
    • Slowly absorbed after IM injections
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6
Q

Estrogens

Pharmacokinetics

A
  • Absorbed orally
    • PO admin ⇒ high ratio of hepatic to peripheral effects
      • ↑ Clotting factors and angiotensinogen
  • Transdermal patch avoids first pass metabolism
  • Highly bound to sex steroid-binding globulin
    • Widely distributed
    • Concentrated in fat
  • Metabolized in the liver
    • Ultimately conjugated to sulfate and glucuronide groups
    • Enzyme inducing agents (phenytoin, rifampin) ⇒ ⊕ phase I metabolism of estrogens
  • Undergo enterohepatic cycling
    • Conjugated estrogens excreted into bile
    • Converted to free estrogen by intestinal bacteria
    • Free estrogens reabsorbed
    • Abx that disrupt intestinal bacteria ⇒ ⊗ enterohepatic circulation
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7
Q

Estrogens

Clinical Uses

A
  • Replacement therapy: failure of ovarian development or removal of ovaries; hypopituitarism
  • HRT in postmenopausal women
  • Combined w/ progesterone analogue: oral contraception, acne, dysmenorrhea, endometriosis
  • Palliative for androgen dependent prostate cancer
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8
Q

Estrogen

Adverse Effects

A
  • Nausea, breast tenderness, edema
  • ↑ Skin pigmentation, esp. in dark skinned women
  • Migraine, headache
  • HTN (d/t ↑ angiotensinogen)
  • Breast cancer ⇒ avoid in women w/ fhx
  • ↑ cholesterol excretion in bile ⇒ ↑ risk of gallstones or another gallbladder disease
  • ↑ Serum-binding proteins (corticosteroid binding globulin, thyroid binding globulin, sex steroid binding globulin)
  • Endometrial hyperplasia/cancer (if used w/o progesterone analogue in HRT)
  • ↑ blood coagulation (↓ Antithrombin III, ↑ factors II, VII, IX, X)
    • 3x ↑ DVT risk
    • Absolute risk is small and not related to age, parity, obesity, or cigarette smoking
    • Risk is significantly ↑ in women who smoke or have other factors that predispose to thrombosis or thromboembolism
  • MI slightly ↑ in women who are obese and greatly elevated in
    those who smoke
    • HTN and DM can ↑ risk
  • ↑ Stroke risk for women over 35 y/o
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9
Q

Progestins

Preparations

A
  • Esters of progesterone
    • Ex. medroxyprogesterone acetate
      • Given PO or IM
      • No androgenic activity
  • 1st gen analogues:
    • Norgestrel and levonorgestrel
      • Some androgenic activity
  • 2nd gen analogues:
    • Norethindrone
      • Intermediate androgenic activity
  • 3rd gen analogues:
    • Desogestrel
      • Lowest androgenic activity
      • Not commonly used d/t ↑ risk of DVT
    • Norgestimate
    • Drospirenone
      • Spironolactone derivative w/ anti-aldosterone and anti-androgenic effects
      • Component of some oral contraceptives
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10
Q

Progestins

Pharmacokinetics

A

Similar to estrogen and its analogues

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11
Q

Progestins

Clinical Uses

A
  • Progesterone esters
    • Used to suppress ovarian function
    • Tx of uterine bleeding
  • Progesterone analogues
    • Used in combination oral contraceptives
  • HRT to ↓ possibility of endometrial cancer
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12
Q

Progestin-only Contraception

A
  • Slows frequency of GnRH pulse generation and blunts LH surge
  • Prevent ovulation in 70-80% of cycles
  • Effectiveness is 96-98%
    • Other factors must play a role
    • E.g. thickening of cervical mucous and atrophy of endometrium
  • Lower progestin content vs combination pills
  • Two formulations: norgestrel (PO or subdermal) and norethindrone (PO)
    • Used by breast-feeding women and those w/ contraindications to estrogens
    • Must take @ exactly the same time every day
      • > 3 hr delay ⇒ back up contraception for 7 days
  • More irregular spotting and bleeding
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13
Q

Progesterone

Adverse Effects

A
  • Hirsutism
    • Less common w/ new progestin agents, newer OC tx
  • Acne
    • High estrogen content improves; androgenic progesterone may exacerbate
  • Weight gain
    • Due to androgen component
  • Glucose intolerance
    • Less common w/ lower doses
  • ↓ HDL and ↑ LDL
    • Less common w/ lower doses
  • Breakthrough bleeding
    • Most common w/ progestin only formulations and low dose formulations
  • Depression
  • Vaginitis and UTI
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14
Q

Combination Oral Contraceptives

MOA

A

Ethinylestradiol + Progesterone analogue

  • CNS effects:
    • Hypothalamus and pituitary (1° site of action) ⇒ ⊗ LH surge ⇒ ⊗ ovulation
    • Basal levels of LH and FSH suppressed in OCP users
  • Urogenital tract effects:
    • Glandular atrophy in the uterine endometrium
    • May ⊗ implantation
  • Progesterone component ⇒ thick cervical mucous ⇒ ⊗ sperm motility and migration
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15
Q

Combination Oral Contraceptives

Administration Regimens

A
  • Monophasic
  • Usu. given for 21 days followed by 7 days of placebo
    • Hormone free interval (HFI) ⇒ ↑ FSH ⇒ menstrual flow
    • Progesterone analogue ⇒ ⊗ estrogenic stimulation of proliferation of the endometrial lining ⇒ lighter menstrual flow
    • Possible ovulation and ↑ estrogen
    • Shorten HFI or add low level estrogen
      • Reduces w/d sx
  • Di and Triphasic
    • Estrogenic component constant
    • Progesterone component initially low but ↑ through the cycle
    • Theoretical advantage = ↓ overall hormones level
    • ? Better for breakthrough bleeding
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16
Q

Monophasics w/ Drospirenone

Combination Oral Contraceptives

A

Yasmin (30 ug Ethinylestradiol + 3 mg drospirenone)

Yaz (20 ug Ethinylestradiol + 3 mg drospirenone)

  • Given over 24 days w/ 4-day hormone-free period
  • Anti-mineralocorticoid activity
    • Counteracts aldosterone-stimulating effects of estrogen
  • Anti-androgenic activity ⇒ less acne and hirsutism
  • Adverse effects:
    • Excess potassium
    • Risk of clots (? More than OCPs): MI, CVA, DVT, PE
  • Falsely claimed better efficacy & failed to communicate risks
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17
Q

Extended

Combination Oral Contraceptives

A
  • Longer cycle formulation
  • 3 on the market:
    • Lybrel (20 ug/ethinylestradiol/90 ug levonorgestrel)
      • Taken for 365 days
    • Seasonale (30 ug/ethinylestradiol/150 ug levonorgestrel)
      • Taken for 84 days then 7 days are hormone-free
    • Seasonique (30 ug/ethinylestradiol/150 ug levonorgestrel)
      • Taken for 84 days then 10 ug ethinylestradiol for 7 days
  • Advantages:
    • Hormone-free interval eliminated to avoid menstruation
      • Less likely to have HA
      • Fewer premenstrual and menstrual sx (breast tenderness, bloating, cramps)
  • Disadvantages:
    • Unscheduled bleeding/spotting
      • ↓ over time
    • Pregnancy may be difficult to recognize
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18
Q

Combination Oral Contraceptives

Adverse Effects

A

Adverse effects are minimal if there are no predisposing factors

In the first 2-3 months of use, AE may include nausea, vomiting, and weight gain

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19
Q

Oral Contraceptives

Absolute Contraindications

A
  • Breast CA or estrogen-dependent neoplasia
  • Abnormal genital bleeding
  • Hx of DVT or PE
  • Hx of CVA or ischemic heart disease
  • Benign or malignant liver tumors
  • Heavy smokers over 35 y/o
  • Women < 6 weeks postpartum who are breastfeeding
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20
Q

Oral Contraceptives

Other benefits

A
  • Regulate periods for pts w/ menstrual disorders such as dysmenorrhea, menorrhagia
  • ↓ Risk of ovarian, endometrial and colorectal cancers
  • Some protection against ectopic pregnancy, ovarian cysts, PID, benign breast lumps and RA
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21
Q

Plan B

[Levonorgestrel]

A
  • Morning-after Contraception
  • MOA is unclear ⇒ may prevent ovulation, transport of the fertilized egg or implantation
  • Must be given within 72 hours of unprotected sex
  • 75-80% effective
    • Effectiveness declines w/ time
  • Most frequent AEs are cramping and nausea
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22
Q

Ella

[Ulipristal acetate]

A
  • Morning-after Contraception
  • Recently came on the market
  • Progesterone receptor modulator
    • Similar in structure to RU-486
  • Effective regardless of the time of the menstrual cycle
  • May be effective as long as 5 days after intercourse
  • AEs similar to levonorgestrel
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23
Q

Insertion of an IUD

A
  • Morning-after Contraception
  • Prevents implantation
  • Requires a visit to the physician
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24
Q

Lunelle

(Contraceptive Injection)

A
  • Non-oral combination contraceptives
  • Contains medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)
  • Administered by IM injection every 28 days
    • First injection is administered 5 days after onset of menstrual period
  • Very effective
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25
Q

Vaginal Ring

(NuvaRing)

A
  • Non-oral combination contraceptives
  • Releases 15 ug of ethinylestradiol and 120 ug etonogestrel daily
  • Worn for 3 out of 4 weeks
  • Some advantages would be constant release, elimination of first pass effect
  • Most common AEs are headache, vaginal discomfort and nausea
26
Q

Contraceptive Patch

(Ortho Evra)

A
  • Non-oral combination contraceptives
  • Contains ethinylestradiol and norelgestromin
  • New patch every wk for 3 wks
  • 4th wk is patch free
  • AEs are mild
    • Similar to oral contraceptives
27
Q

Mirena

A
  • Non-oral progesterone contraceptives
  • IUD containing levonorgestrel
  • Lasts up to 5 yrs
  • Works mainly by thickening cervical mucous
  • After 4 yrs, 75% of cycles were ovulatory
  • In the first 3-6 months, periods are irregular
    • Then ↓ bleeding but may be irregular
    • Significant % of women will have no period
28
Q

Implanon

A
  • Non-oral progesterone contraceptives
  • Implant containing etonorgestrel
  • A single silastic implant under the arm just below the skin
  • Good for 3 yrs
  • Most frequent cause for discontinuation is irregular bleeding
    • Does become more regular w/ continued use
    • Significant % of women will have no period
29
Q

Depo-Provera

A
  • Non-oral progesterone contraceptives
  • IM injection of medroxyprogesterone acetate
  • Lasts for 3 months
  • Causes weight gain
  • May cause ↓ bone density in teenagers and young adults
30
Q

Menopause

A
  • Progressive ↓ estrogen production by the ovary w/ advancing age
  • Partial compensation by conversion of androstenedione precursor
  • Several estrogen-related sx associated w/ menopause:
    • Osteoporosis
    • Vasomotor symptoms (“hot flashes”)
    • Urogenital atrophy
    • Vaginitis
  • HRT can be effective for some sx
  • Reasonable alternatives for some sx
    • Ex. clonidine for hot flashes
  • Estrogen no longer used to prevent development of cardiovascular disease
31
Q

Osteoporosis

A
  • Loss of calcium phosphate and colloid protein matrix of bone
    • Thin brittle bones, compression fx of vertebrae, hip and wrist fx
    • Major health concern
  • Requires continuous use of estrogen
    • Start tx ASAP b/c estrogen not as effective at restoring bone that is already lost
  • Usually used w/ dietary calcium and vitamin supplements
  • Weight bearing exercise also good
  • Other potential tx:
    • Raloxifene
      • Tissue selective estrogen receptor antagonism/agonism
        • Agonist activity in bone and on lipid metabolism
          • Preserves bone mineral density and ↓ LDL cholesterol
        • Antagonist activity on the uterus and breast tissue
          • ⊗ Breast epithelium and uterine endometrium proliferation
      • Contraindicated in pts w/ a hx DVT or PE
      • May ↑ hot flashes
    • Allendronate
      • Bisphosphonate derivative
      • ⊗ Osteoclast-mediated bone-resorption
32
Q

Hormone Replacement Therapy

Regiments

A
  • Intact uterus ⇒ estrogen/progestin combo
    • Progestin analogue ⇒ prophylaxis vs endometrial hyperplasia or carcinoma in estrogen treated women
    • Most commonly used estrogen is conjugated estrogen
    • Most commonly used progestin is medroxyprogesterone
  • No uterus (Hysterectomy) ⇒ estrogen alone
    • Endometrial cancer is not a concern
    • Cyclic therapy
      • Estrogen for 28 days
      • Add medroxyprogesterone the last 14 days
      • Withdrawal bleeding occurs
      • Premphase contains 28 tablets of conjugated estrogen and 14 tablets of medroxyprogesterone
    • Continuous regimen
      • Estrogen and progestin given daily
      • Prempro is monophasic 28 tablets of conjugated estrogen and 28 tablets of medroxyprogesterone
    • Transdermal patches or vaginal rings
33
Q

Hormone Replacement Therapy

Risks vs Benefits

A
  • WHI trial ended at 5.2 yrs
  • Specific to women treated w/ combo of conjugated estrogen + medroxyprogesterone acetate
  • For every 10k women per year:
    • 8 more got breast CA
    • 7 more got CAD
    • 8 more had a stroke
    • 8 more had PE
    • 10 more had DVT
  • Some risk factors did ↓:
    • 6 fewer had colorectal CA
    • 5 fewer had hip fx
    • Benefits are very small relative to the risks, when taken chronically
    • Estrogen and progestin should not be used to prevent coronary heart disease
  • Some unresolved issues:
    • Effect of estrogen alone or effect of other doses or routes of admin
    • Risk benefit ratio for shorter term use
    • Role in improving QOL and/or cognitive function
34
Q

Leuprolide

A
  • Exogenous GnRH ⇒ continuous admin
    • Down regulation of receptors in the pituitary
    • Shuts down hypothalamic pituitary axis
  • Tx prostate cancer and endometriosis
  • Prevent premature LH surges in ovarian hyperstimulation protocols
35
Q

Ganirelix

A
  • GnRH antagonist
  • Theoretical advantages over agonists
    • Absence of “flare response”
    • No GnRH receptor down regulation
    • ⊗ LH/FSH release almost immediately
      • Degree of suppression depends on circulation levels of GnRH antagonist
    • Dose proportionality
36
Q

GnRH and GnRH Antagonists

Indications

A
  • Endometriosis (not tx of choice)
  • Prostate CA
  • Ovarian hyperstimulation
  • Male infertility (agonists)
37
Q

Ovarian Hyperstimulation

A
38
Q

Gonadotropins

A

⊕ Ovulation in controlled ovarian hyperstimulation

Can cause ovarian hyperstimulation syndrome and multiple pregnancies

39
Q

Bromocriptine

A

Dopamine agonist

Treat Parkinson’s and hyperprolactinemia

40
Q

Oxytocin

A

⊕ Uterine contractions

41
Q

Androgens

Preparations

A
  • Synthetic androgens and Anabolic agents
    • (17-alkyl-substituted steroids)
    • Androgens w/ equal (1:1) androgenic/anabolic activity
    • Testosterone replacement therapy
  • Some analogues have anabolic activity > androgenic activity
    • Methyltestosterone
    • Oxandrolone
    • Nandrolone
42
Q

Androgens

Clinical Uses

A
  • Androgen replacement therapy
    • Men w/ hypogonadism (both 1° and 2°)
    • Testosterone can be given IM or transdermal
  • Protein anabolic agent
    • Androgens and anabolic steroids
    • Used in conjunction w/ dietary measures and exercise
    • Reverse protein loss after trauma, surgery or prolonged immobilization
  • Abuse in sports
    • Use of anabolic steroids by athletes
    • ↑ Strength and aggressiveness, improving competitive performance
      • Demonstrated in women
      • Not unequivocally demonstrated in men
    • Adverse effects makes their use inadvisable
43
Q

Androgens

Adverse Effects

A
  • Women:
    • Masculinization
    • Deepening of the voice
    • Hirsutism
    • Clitoral enlargement
    • Amenorrhea
    • Admin of androgens to pregnant women ⇒ ± masculinization of external genitalia in female fetus
  • Men:
    • Gynecomastia
    • Azoospermia
      • ↓ Testicular size
      • Supraphysiologic doses of androgens ⇒ ⊗ LH and FSH
      • May take months to recover after cessation of therapy
  • Both male and female:
    • ↓ Pituitary and adrenal function
    • Acne
    • ↑ Aggressiveness and psychotic sx
    • Sleep apnea
    • Erythrocytosis
    • Sodium retention and edema
      • Watch for in pts w/ heart and kidney disease
    • Short stature
    • Lower HDL
    • Hepatic Dysfunction
    • ↑ Aminotransferases
      • Usu. occur early & dose-dependent
    • Cholestatic jaundice
    • Peliosis hepatis (blood-filled lacunae in liver parenchyma)
    • Hepatocellular carcinoma
  • Young steroid abusers:
    • MI
    • Arrhythmic death
    • CVA
    • (↓ HDL, ↑ cholesterol)
  • Contraindicated in pts w/ underlying prostate carcinoma
44
Q

Finasteride

A

“Propecia, Propecia Pro-Pak, and Proscar”

  • Type II 5-α-reductase inhibitor
  • ⊗ Testosterone → dihydrotestosterone in the prostate
  • Used for BPH and male pattern baldness
  • May be used w/ α-blockers
45
Q

Flutamide

A
  • Non-steroidal antiandrogen
    • Binds androgen receptor ⇒ antagonist-receptor complex that does not undergo activation
  • Treats prostate cancer, hirsutism
  • Treats “flare response” when GnRH analogues used to tx prostate cancer
  • AE:
    • Hepatic failure
    • Hot flashes
    • Gynecomastia
46
Q

Spironolactone

A
  • Aldosterone antagonist ⇒ tx hyperaldosteronism
  • K+ sparing diuretic ⇒ tx CHF
  • Weak androgenic receptor antagonist
  • ⊗ Cytochrome p450 ⇒ ↓ testosterone synthesis
    • ↓ ⊖ feedback by testosterone ⇒ ↑ GnRH secretion
  • Not used for prostate CA
  • Used for PCOS and hirsutism (off label)
  • Causes gynecomastia
47
Q

Ketoconazole

A
  • Broad spectrum antimycotic (usu. used topically)
  • Higher PO doses ⇒ ⊗ testosterone in prostate cancer pts when other tx ineffective
  • May be used in Cushing’s (↓ glucocorticoid synthesis)
48
Q

Selective Estrogen Receptor Modulators (SERM)

A
  • Many estrogen receptor antagonists have agonist-like effects in some tissues
  • Accounted for by complexity of estrogen receptor signal transduction system
    • 2 types of estrogen receptors
    • Transcriptional coactivators and corepressors
49
Q

Tamoxifen

A

Selective Estrogen Receptor Modulator (SERM)

  • Antagonist in breast tissue
  • Partial agonist in the endometrium
    • Monitor for endometrial carcinoma
  • Used to tx breast CA, esp. those positive for estrogen receptor
    • Prevent redevelopment of cancer after surgery
    • Reduce incidence of CA in contralateral breast
  • Side effects: DVT, hot flashes, weight gain due to fluid retention, mild nausea
50
Q

Raloxifene

A

Selective Estrogen Receptor Modulator (SERM)

  • Estrogen receptor agonist at bone
  • Antagonist in breast and endometrial tissue
  • Used to treat osteoporosis
  • May be effective for invasive breast CA w/o side effects of endometrial carcinoma
  • Side effects are similar to tamoxifen
    • DVT, hot flashes, weight gain due to fluid retention, mild nausea
51
Q

Clomiphene

A

Selective Estrogen Receptor Modulator (SERM)

  • Antagonist in the hypothalamus and pituitary
  • Agonist in the ovary
  • Indirect acting:
    • ⊕ Ovulation in infertile women w/ functional HPA and adequate estrogen levels
    • Opposes ⊖ feedback by estrogen @ hypothalamus
      • ↑ GnRH pulse frequency ⇒ ↑ FSH and LH ⇒ ⊕ follicle development ⇒ ↑ estrogen ⇒ LH surge ⇒ ovulation
  • Side effects:
    • Ovarian enlargement
    • Hot flashes
52
Q

Danazol

A
  • Weak partial agonist @ progestin, androgen and glucocorticoid receptors
  • ⊗ GnRH release ⇒ indirectly ⊗ estrogen synthesis
  • Tx endometriosis and fibrocystic disease of the breast
  • Side effects related to androgenic and glucocorticoid receptor stimulation
    • Weight gain, edema, ↓ breast size, acne, oily skin, hair growth, deep voice, etc.
53
Q

Anastrozole and Letrozole

A
  • Aromatase inhibitors
    • ⊗ Estrogen synthesis
  • Treats metastatic breast cancer that is resistant to estrogen receptor antagonists
    • Equal efficacy to tamoxifen w/ less toxicity
    • Does not cause endometrial carcinoma
  • AEs:
    • Hot flashes, nausea
    • ↑ Bone resorption
    • ↑ LDL
54
Q

Fulvestrant

A
  • Selective estrogen receptor down regulator (SERD) and
  • *potent antiestrogen**
  • Immobilizes ER-α in the nuclear matrix ⇒ receptor polyubiquitination ⇒ degradation via 26S proteasome
  • Depends on interaction of ER-α w/ cytokeratins 8 and 18 (CK8/CK18)
  • Used for estrogen receptor-α ⊕ breast CA after other anti-estrogen tx have failed
55
Q

Mifepristone

(RU-486)

A
  • Competitive progesterone antagonist
  • Used to induce abortion
  • Progesterone needed to maintain pregnancy, esp. the uterine lining
    • ⊗ Progesterone ⇒ blastocyst death ⇒ ↓ human chorionic gonadotropin (hCG) ⇒ corpus luteum involution
  • Used in combo w/ misoprostol (prostaglandin analogue) ⇒ ⊕ uterine contractions
  • Potential complication is excessive vaginal bleeding
56
Q

Diethylstilbestrol

A
  • Diphosphate ester injection
    • Oral preparations are no longer available
  • Non-steroidal analogue of estrogen
    • Less rapidly inactivated than natural estrogens
  • Originally used to treat habitual abortion
  • No longer used b/c in utero exposure associated with:
    • Structural abnormalities in the cervicovaginal area and/or uterine cavity
    • ↑ Risk of developing clear-cell adenocarcinoma of vagina/cervix
  • Not the drug of choice for any indication
57
Q

Estrogens Table

A
58
Q

Progestins Table

A
59
Q

HPA Hormones

Table

A
60
Q

Androgens & Antiandrogens

Table

A
61
Q

SERMs and Other Agents

Table

A

6. HDS GI Repro (30 decks)

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