8. female reproductive pharmacology

Therapeutic Uses

• Menopausal hormone therapy

• Cancer hormono-therapy

• Acne & female hypogonadism

Kinetics

• Admin PO, transdermal, intravaginal, parenteral

• CYP450 metabolism

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

selective estrogen-receptor modulators

- antagonist in some tissues

- agonist in other tissues

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

- 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

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

When combined with estrogen,• Higher risk of breast cancer• Higher risk of thromboembolic events

Also:

• Abdominal discomfort

• Breast tenderness

• Irregular menses

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

Heart Disease

• MHT increases risk of cardiovascular events

Alzheimer’s Prevention

• No conclusive evidence MHT delays Alzheimer onset

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

young females

those without a uterus -> no risk for endometrial cancer

• Strong rebound vasomotor symptoms• No data on gradual tapering vs. immediate cessation

• Only decrease estrogen• Keep progestin levels the same until estrogen at 0

extremely effective: surgery, IUDs

very effective: OC, patch, ring, intramuscular depo

effective: condoms

least effective: sponge, spermicide

theoretical: if we were all robots

actual: issues with adherence

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

essentially make hormones a flat line, no fluctuations:

- Inhibits FSH, ↓ follicular maturation

- Inhibits LH surge, causing anovulation

- Alters endometrium, ↓ implantation

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

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