what are therapeutic uses + kinetics of estrogens?
Therapeutic Uses
• Menopausal hormone therapy
• Cancer hormono-therapy
• Acne & female hypogonadism
Kinetics
• Admin PO, transdermal, intravaginal, parenteral
• CYP450 metabolism
what are estrogens ADRs? interactions? contraindications?
Adverse Effects
• Endometrial dysplasia/cancer ➢ Mitigate via Concurrent admin of progesterone
• Jaundice, Nausea, Migraine headache
Interactions
CYP450 inducers/inhibitors
Reduces efficacy of Antidiabetic Rx, Thyroid replacement, Anticoagulants
Contraindications
Deep vein thrombosis
Pulmonary embolism
Stroke/myocardial infarction
Liver disease
Estrogen-dependent tumors
Pregnancy
what are SERMs?
selective estrogen-receptor modulators
- antagonist in some tissues
- agonist in other tissues
what are uses of Raloxifene? actions? toxicity?
Therapeutic Uses
• Postmenopausal osteoporosis
• ER-Positive Breast cancer prevention
Actions
• Agonist for bones, lipid metabolism & blood clotting
• Antagonist for breast & endometrium
Toxicity Black Box Warning:
Deep Vein Thrombosis & Pulmonary Embolism
Discontinue if prolonged immobility (ex. travel, surgery)
Very Serious Teratogen
• Completely contraindicated during pregnancy
what are the differences between estrogen and raloxifene?
- E. increases BMD and reduces fracture risk MORE
- E: raises HDL cholesterol, R. does not
- R: protects against breast cancer, E increases risk
- R does not promote endometrial cancer, E. increases risk of endometrial
- E. alleviates menopausal symptoms, R does not
- R. causes bleeding in 3-5% of postmenopausal, E. causes in 45%
- BOTH have same black box working
what are therapeutic uses + kinetics of progestins?
Therapeutic Uses
• Menopausal hormone therapy- Only to reduce estrogen-related endometrial cancer risk
• Dysfunctional uterine bleeding- To reduce hemorrhage, promote regular monthly cycle
• Also, against amenorrhea, infertility & prematurity prevention
Kinetics
• Multiple admin routes available: PO, transdermal, intravaginal, parenteral
what are ADRs of progestins?
When combined with estrogen,• Higher risk of breast cancer• Higher risk of thromboembolic events
Also:
• Abdominal discomfort
• Breast tenderness
• Irregular menses
what are approved indications for menopausal hormone therapy (MHT)?
moderate/severe vasmotor symptoms
- they decrease over time
- MHT is safe for short term use
- if contraindicated, use Paroxetine (SSRI less effective tho)
moderate/severe vulva + vaginal atrophy
- use topical estrogen: minimize toxicity, allows long term use
osteoporosis prevention
- only for high risk females
- life long therapy increases risks of MHT
what is inappropriate use of MHT?
Heart Disease
• MHT increases risk of cardiovascular events
Alzheimer’s Prevention
• No conclusive evidence MHT delays Alzheimer onset
what are the benefits vs risks of estrogen + progestin? estrogen only?
benefits: less T2DM, colorectal cancer, osteoporotic fractures
risks: breast cancer, cholecystitis, thromboembolism
benefits: less T2DM, CHD, osteoporotic fractures, breast cancer
risks: cholecystitis, endometrial cancer, thromboembolism
who are safest groups for MHT?
young females
those without a uterus -> no risk for endometrial cancer
how does discontinuing hormonal therapy happen?
• Strong rebound vasomotor symptoms• No data on gradual tapering vs. immediate cessation
• Only decrease estrogen• Keep progestin levels the same until estrogen at 0
what are different groups of birth control?
extremely effective: surgery, IUDs
very effective: OC, patch, ring, intramuscular depo
effective: condoms
least effective: sponge, spermicide
what is actual use vs theoretical use?
theoretical: if we were all robots
actual: issues with adherence
how do you pick the right contraceptive?
Consider effectiveness / safety / family planning / personal preferences /
Sterilization (vasectomy & tubes ligation) = Most effective but bad option if family goal not achieved
Convenience & accessibility → OCs & Condoms most popular
Females 35+ smoking or high risk of thromboembolic events → Avoid Combination OCs
Frequent sexual intercourse or accessibility issues → Long-term contraceptive (ex: implants)
Infrequent intercourse → Condoms & spermicides → No systemic toxicity
Multiple sexual partners/non-monogamy (higher risk of STBI) → Avoid IUDs + Favor Condoms
how do combination OC pills work?
essentially make hormones a flat line, no fluctuations:
- Inhibits FSH, ↓ follicular maturation
- Inhibits LH surge, causing anovulation
- Alters endometrium, ↓ implantation
what is OC effectiveness + safety?
Effectiveness
• Theoretical ≈ 99.7%• Actual ≈ 92%• Even lower efficacy in individuals with higher-BMI/higher fat % -> pill gets dispersed throughout, + due to high adipose tissue, there is more estrogen production
Overall Safety
• Very good• Oral contraceptive mortality < pregnancy & delivery mortality• Compared to other contraceptives: broader range of adverse effects
what are contraindications of OC?
absolute:
- anything thrombo
- abnormal liver function
- known/suspected breast cancer
- undiagnosed abnormal vaginal bleeding
- known/suspected pregnancy
- smokers over age of 35
- pregnancy
relative
- hypertension
- diabetes
- migraine
- epilepsy
- cardiac disease
- uterine leiomyoma