223. Repro Pharm

Question 1

DA Agonists

• names
• function
• use
• which one is better

Answer 1

Bromocriptine and Cabergoline
fx: inhibit PRL (DA agonists)
Use: hyperPRL (menstrual irregularity, infertility, galactorrhea) because PRL inhibits GnRH; decrease size of prolactinoma
Cabergoline: fewer GI SE and longer acting = USE FIRST
Bromocriptine: shorter acting: use when trying to get PREGNANT than STOP AT CONCEPTION

Question 2

Treatment for PCOS

• Clomiphene Citrate: mechanism
• Tamoxifen: mechanism
• Letrozole: mechanism
• Metformin: mechanism
• Medroxyprogesterone Acetate: mechanism

Answer 2

Clomiphene Citrate: SERM; ovulation induction
E-antagonism: brain (perceive low E, neg fb more E more FSH, more follicles, more E, more ovulation), cervical mucus/endometrium atrophy

Tamoxifen: SERM, reduce breast cancer, induce ovulation
E-antagonism: breast (less cancer), causes hot flashes (low E)
E-agonism: Predisposes VTE, maintains BMD, supports vaginal mucosa, endometrial proliferation (higher endometrial Ca)

Letrozole: aromatase inhibitor (more negative fb = more FSH)

• indication: adjuvant tx breast cancer, off-label go-to med to induce ovulation in PCOS
• shorter half life and less anti-E effects than clomiphene (better for endometrium)

Metformin: less hepatic glu production/gluconeogenesis = less ins release = less androgen production from theca cells (ins binding to theca cells increases androgen production) - remove hyperandrogenism to induce ovulation

Medroxyprogesterone Acetate: Progestin, used for cycle control, cycles uterine lining, contraception (prevent unopposed E stim in PCOS)

Question 3

Birth Control

• what type of E do we use
• what generations of P are there
• what combination is best and what are its effects (2)

Answer 3

E: Ethinyl Estradiol (10-35mcg)
P: 1st Gen (Norethindrone - binds T receptors), 2nd Gen (norgestrel - binds T-r), 3rd gen (Norgestimate - less androgenic), Drospirenone (spironolactone activity, anti-androgen), Dienogest (strong anti-androgen activity)

Combo: Ethinyl Estradiol + Progestin
PCOS: less ovarian androgen production by inhibiting FSH/LH, more E increases SHBG = less free T (less acne, less hirsutism, cycle control - less endometrial hyperplasia risk)
P Effects: less ovulation, less ovarian hormone production, less thick endometrial lining, thicken sperm mucus (impede sperm transit)

Hormone Withdrawal bleeding is NOT Menstrual - lining shed during placebo week = lighter

Question 4

Menopause/Ovarian Failure Tx

• HRT
• Improve fertility in mp tx
• Premarin
• Raloxifene: mechanism, use

Answer 4

HRT: induce puberty in premature ovarian failure, relieve hypo-E sx if early pre-mp (VMS, VVA, low BMD)

NO TX to improve fertility = need oocyte donation

Premarin: conjucated E for HRT (may increase risk for endometrial cancer)

Raloxifene: SERM
use: prevent/tx OSTEOPOROSIS, reduce breast cancer risk
E-antagonism: breast (less cancer), causes VMS, VVA
E-neutral at endometrium: no effect
E-agonism: VTE, maintains BMD

Question 5

Injectables

• Gonal-F/Follistim: use
• GnRH agonists: mechanism, use, SE
• injectable hCG: mechanism, use
• 5a-Reductase Inhibitor: mechanism, use

Answer 5

Gonal-F/Follistim: recombinant FSH
- use: hypothalamic amenorrhea (increase fertility), IVF to rescue follicles (need GnRH agonists to block LH premature surge)

GnRH agonists: cause desensitization: uncoupling of receptor/signaling pathway, downregulate receptors

• uses: Women: suppress LH surge in IVF sampling, endometriosis, fibroids, breast cancer; Men: Prostate Cancer; All: ARREST puberty (precocious puberty tx)
• SE: may have initial effect 1st 2 weeks (stim FSH/LH), Women: VVA, VMS (low E/P), Men: ED (low T), All: low BMD (low E)

Injectable hCG: binds LH-R

use: trigger ovulation, oocyte final maturation, follicle cumulus expands
use: assistive reproduction, cryptorchidism (increases T), male hypogonadism (increases T)

5aR Inhibitors: lower DHT (potent androgen)
use: prostate cancer, BPH, Male Pattern Baldness, Hirsutism in women

Question 6

What are the anti-estrogens you would use for breast cancer? Prevention vs. Tx. Why?

Answer 6

E causes proliferation of breast epithelial cells

Prevention: SERMS (Tamoxifen, Raloxifene)

Tx: GnRH agonists: Goserelin Acetate
SERMS: Tamoxifen + Raloxifene
Aromatase Inhibitor: Anastrozole, Letrozole