Therapeutic Sex Hormone Flashcards

Question

Vaginal Ring | (NuvaRing)

Answer 1

* 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**

Answer 2

* Non-oral _combination_ contraceptives * Contains **ethinylestradiol** and **norelgestromin** * New patch every wk for 3 wks * 4^th wk is patch free * AEs are mild * Similar to oral contraceptives

Answer 3

* 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

Answer 4

* 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

Answer 5

* 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

Answer 6

* 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

Answer 7

* **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**

Answer 8

* _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**

Answer 9

* **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

Answer 10

* **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

Answer 11

* **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**

Answer 12

* Endometriosis (not tx of choice) * Prostate CA * Ovarian hyperstimulation * Male infertility (agonists)

Answer 13

**⊕ Ovulation** in _controlled ovarian hyperstimulation_ Can cause **ovarian hyperstimulation syndrome** and **multiple pregnancies**

Answer 14

**Dopamine agonist** Treat Parkinson’s and hyperprolactinemia

Answer 15

⊕ Uterine contractions

Answer 16

* **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**

Answer 17

* **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

Answer 18

* _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**

Answer 19

"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**

Answer 20

* **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**

Answer 21

* **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**

Answer 22

* 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**)

Answer 23

* 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**

Answer 24

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**

Answer 25

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**

Answer 26

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**

Answer 27

* **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.**

Answer 28

* **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**

Answer 29

* **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

Answer 30

* **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**

Answer 31

* **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