Endocrine: Sex Hormones Flashcards
Clomiphene
SERM and estrogen antagonist at hypothalamus
Indications of clomiphene
- Anovulatory infertility
2. Oligospermia infertility
S/Es of clomiphene
- Multiple pregnancies
- Hot flushes
Hot flushes because FSH and LH are vasodilatory
Centchroman other name
Ormeloxifene
Ormeloxifene action and indications
Estrogen receptor ANTAGONIST at ENDOMETRIUM
Indication: OCP, non-steroidal
Ospenifene indication
Post menopausal dyspareunia
Fulvestrant
- parent class
- MOA
- site of action
- indication
- RDA
- SERD: selective estrogen receptor downregulator
- Inhibits ER dimerization. Hence, increases its degradation
- Breast: selectively downregulates breast estrogen receptors
- Breast cancer: ER positive, tamoxifen resistant
- Monthly, i. m. in the butt
Tibolone
- parent class
- MOA
- indications
- STEAR: selective tissue estrogen activity regulator
- metabolites exert estrogenic, progestational, weak androgenic effects in specific tissues
- designer HRT: relieves osteoporosis and vaginal atrophy with no increased cancer effect on breast and endometrium
Third generation AIs
- Letrozole
- Anastrozole
- Exemestane
AI indications
Postmenopausal breast cancer
Because aromatisation is the major source
Generations of progesterone
1st Norethindrone
2nd Levonorgestrol
3rd Norgestimate
4th Drospirenone
Pregesterones are usually androgenic. Name an anti-androgenic progesterone? Indications?
Drospirenone (of spironolactone group)
Indications
- combined OCP
- moderate acne (FDA app)
- PMS dysphoria (FDA app)
SPRM examples
Selective progesterone receptor modulator
Mifepristone
Onapristone
Ulipristal
Uses of mifepristone
Mm: MIFEPrIstone
Morning after pill (emergency contraceptive)
Induction of abortion ( <49 days)
Fibroids
Endometriosis
PR positive cancers : breast cancer, meningioma
Increased steroids (Cushing syndrome)
tone
Mife is an antagonist at ?
- Progesterone receptor
- Androgen
- Glucocorticoid
Onapristone MOA and indications
MOA: antagonist at PR of endometrium ONLY
Indication: induction of abortion
Ulipristal indication
Emergency contraceptive
Exclusive actions of testosterone (not shared by dihydrotestosterone)
Shared actions
Mm: FISH
Feedback inhibition
Internal sex organs
Spermatogenesis
Hematopoeisis
Shared: Secondary sex characters, anabolic effects
Exclusive actions of testosterone are despite DHT having a higher affinity for androgen receptor than testosterone
Harmful effects of excess testosterone
- BPH
2. Prostate cancer
Drugs for BPH and Prostate cancer
BPH: 5 alpha reductive inhibitor
- finasteride
- dutasteride
Prostate cancer: androgen receptor blocker
- flutaminde
- nilutamide
- bicalutamide
Androgen RBs are stronger than 5 alpha RBs
Finasteride in BPH
Given for static component. Hence, takes 3-5 months for action.
Tamsulosin is for dynamic component. Acts immediately and gives symptomatic relief
Indications and ADRs of 5 alpha reductive inhibitors
Indications
- BPH
- Androgenital alopecia
ADRs
-impotency
Quantity used to compare testosterone and anabolic steroids
Androgen: Anabolic ratio
T- 1:1
Ana Ster- 1:2 to 1:3
Anabolic steroids examples
Nandrolone
Stanozolol (not a beta blocker)
Indications and Side effects of anabolic steroids
No clinical indications. Only abused by athletes
- cholestatic jaundice
- BPH and Prostatic cancer
Disadvantages of anabolic steroids
- short lasting effect
- unreliable (might be absent)
- ADRs
- cholestatic jaundice
- BPH and prostate cancer
Main MOA of
- combined OCP
- POP/ mini pills
- emergency contraceptive
- combined: inhibit ovulation by feedback inhibiting LH
- POP: thicken cervical mucus
- emergency contraceptive: inhibit implantation
Most common OCP combination
Ethinyl estradiol 30-40 ug
Norethindrone 1000 ug
Now we use 2nd/3rd gen progesterone
Cause of breakthrough bleeding while on COMBINED OCP
Less estrogen endogenously
Management of breakthrough bleeding
Theoretically, increase estrogen or decreases progesterone.
Increasing estrogen incurs side effects. Hence, we decrease progesterone by switching to biphasic and triphasic pills, which mimic the gradual increase in progesterone concentration.
Indications of POP
When estrogen is contraindicated eg. Past Hx of
- DVT, VTE
- MI
- Lactation (estrogen inhibits lactation)
Drug given in POP
Levonorgestrel 1 tab daily
Examples of emergency contraceptives
- C OCP- 2 tabs stat and 2 tabs after 12 hours
- POP- levonorgestrel 1.5 mg stat
- Mife- 600mg stat
- Ulipristal- 30mg stat (up to 5 days post coitus)
Mild ADRs of OCP
Mm: NORMAL
Don’t warrant withdrawal
Nausea Oedema Recurrent headache Mastalgia Abnormal bleeding Loss of withdrawal bleeding (amenorrhea for first few cycles)
Moderate ADRs of OCP
Can stop but not necessary
Include the androgenic side effects of progesterone
- Acne
- Wt gain
- Chloasma
Severe ADRs of OCPs
Mm: 4 C’s
CNS: depression
CVS: thromboembolism like DVT, PE, MI, stroke
Cholestatic jaundice
Cancer: breast and cervical
Benefits of OCPs
Mm: Other BENEFITS
Decreases risk of the following
Ovarian cyst- is decreased (DOC in PCOD) Benign breast disease- fibrocystic disease Endometriosis Neoplasia- endometrial and ovarian Ectopic pregnancy (copper T increases risk) Fibroids Tension syndrome (PMS) Skeletal disease- osteoporosis
