Women's Health - PHARM

Ovaries produce estrogen.

What converts it to its most active form, estradiol?

What is the other E molecule?

aromatase // Ethinyl estradiol

menopausal sx is the result from a decr. in E:

What are some examples of vasomotor, bone effects, lipid effects, coginitive effects?

Vasomotor symptoms:

• hot flashes

• night sweats

• Urge incontinence frequency

• UTIs

• dryness

• dyspareunia

• Female sexual arousal disorder

• Osteoporosis bone loss

• Altered lipids: incr LDL / decr HDL

• difficulty problem-solving / short-term memory loss

What is the physiological effect of E?

• ductal growth in breast

• vaginal epithelium thickening

• uterine proliferation

• blocks bone resportion

• decr. vasoconstriction 

• incr. perfusion

• decr. LDL / incr. HDL

• preserves cognitive fct, regulates mood

What are key ADE of estrogen therapy?

• Endometrial hyperplasia // Endometrial cancer

• Thromboembolic risk

• Nausea (improves with use)

• HA (migraines)

• Fluid retention

What are clinical indications for Rx E?

• Contraception (stronger dose than HRT)

• Menopausal HRT

• female hypogonadism

• Acne in young females

• Gender transition therapy (off-label)

When is estrogen C/I?

• if unopposed E Rx: Intact uterus

• ER (+) breast cancer / unexplained vaginal bleeding

• History of DVT / PE /Stroke / MI / 1st 21 days postpartum

• CVD / high risk

Which estrogen routes reduce clot risk compared to PO?

Transdermal form (spray / gel / patch / emulsion)

Intravaginal cream or ring for local effects – Parenteral IV for acute heavy uterine bleeding only

List other forms of E aside from transdermal:

• MC = PO

• intravaginal (cream qhs OR ring for q3mos)

• IV (acute EMR ctrl for heavy uterine bleeding)

tamoxifen, raloxifene, and bazedoxifene are what class of drugs?

Selective E Receptor Modulators (SERMs)

Selective E Receptor Modulators (SERMs) has “tissue selective MOA”, expand upon the general concept.

agonist in some (produces benefits) // antag. in some (prev. harmful effects)

What is tamoxifen’s MOA and an indication for its use?

ER antag in breast tissue // agonist in bone (protects against osteoporosis) & endometrium

• tx active breast Ca

• prophylactic in high-risk pt.

What is raloxifene’s indication?

osteoporosis prev. + tx in post-menopause (≠ 1st line)

What drug is used to tx menopausal sx in those w/ an intact uterus?

Bazedoxifene!

Synthetic progestins are used b/c they are more stable, what is the PK of natural progesterone?

rapid metabolism

What progestin effects occur during menstrual cycle?

• Drop in levels triggers menstruation

• Stimulates breast epithelium growth

• depression and sleepiness

• Raises body temp. at ovulation by about 1 degree F

What progestin effects occur during pregnancy?

• Suppress uterine smooth muscle contractions (maintains pregnancy)

• Suppress GI smooth muscle contraction → C

• Promote alveolar tubule growth (lactation prep)

What are main uses of progestins?

• counteracts ADE of E (in HRT)

  • dysfct uterine bleeding (severe bleeding d/t continuous proliferation on E) 

• Contraception

• Supporting early pregnancy

What are ADE of progestins?

• HA

• Depression

• Weight gain

• Libido changes

• Breast tenderness

• incr breast cancer risk (when combined with estrogen in post-menopause) — WATCH LECTURE

What are C/I for progestins?

• Unexplained vaginal bleeding

• History of thromboembolic dx

• Active liver disease

• Breast cancer

What are forms of progestin?

• PO

• IM

• SQ

• Intravaginal

• Transdermal

Indications for HRT?

• low dose sys. — tx vasomotor sx

  • alt: SSRI / SNRI / clonidine

• GU sx

• prev. of post-menopausal high-risk osteoporosis (long-term)

  • not 1st line!

Which HRT regimens are used considering uterus status?

Intact: Estrogen plus progestin

Absent: Estrogen only

ACOG says some research has shown benefits for decr. risk of MI if starting combined HRT w/n 10 yrs of menopause 

BUT what does the USPSTF say?

USPSTF states the long-term use for prev. does NOT outweight the risk

Venlafaxine incr. serotonin / norepi, how does that help vasomotor sx?

regulates body temp

Paroxetine incr. serotonin, how does this help vasomotor sx?

body temp regulation 

what drug blocks a signal in the brain’s thermoregulatory center → blocks the trigger for vasomotor sx?

fexolinetant = neurokinin 3 receptor antag.

Which central alpha-2-adrenergic receptor agonist can be used for vasomotor sx?

clonidine: decr. sympathetic ctrl of blood vessels

What are non-hormonal tx for vaginal dryness?

lubricants / moisturizers

T/F: no need to taper HRT

FALSE. taper slowly (dose or day) — decr. E / P remains the same

What are HRT risks and precautions?

Use lowest dose for shortest duration – Not for CVD prevention – Caution in women over 60 or more than 10 years past menopause — WATCH LECTURE

What are adverse effects of SERMs?

Hot flashes – Leg cramps – Risk of VTE – Tamoxifen increases risk of endometrial cancer —> watch lecture

What is the main mechanism of estrogen in contraception?

Suppress FSH release – Stabilize endometrium

What meds are used in transgender women therapy?

• Estrogen

• Anti-androgens (ex. spironolactone)

What meds are used for female sexual interest or arousal disorder?

Flibanserin / Bremelanotide

What meds are used in transgender men therapy?

Testosterone formulations IM SQ transdermal – Contraception may still be required

What is flibanserin’s indications for females?

• low libido (≠ asso. w/ medical / mental dx)

• qd for several weeks to see benefits

  • D/C if ≠ improvement after 8 wks

Why is Flibanserin Rx through a REMS program?

• hypoTN and syncope

• BBW: D/C alcohol for 2+hrs before → up to next morning

What is bremelanotide’s MOA, PK, C/I?

• Melanocortin receptor agonist

• SQ injection 45 mins prior → max 8x/month

• C/I: unctrl HTN / CVD dx

What is the main mechanism of progestin in contraception?

Suppress LH surge prevent ovulation – Thicken cervical mucus – Atrophy endometrium

What are benefits of combined oral contraceptives?

Cycle regulation – Less dysmenorrhea – Less acne – Decreased ovarian and endometrial cancer risk

What are adverse effects of combined oral contraceptives?

Nausea – Breast tenderness – Breakthrough bleeding – Increased risk of VTE – Stroke – MI – Especially in smokers over 35

What are contraindications for combined oral contraceptives?

History of VTE – Stroke – CAD – ER positive breast cancer – Migraines with aura – Smokers over 35 – Severe HTN – Active liver disease

What are non-oral hormonal contraceptive options?

Transdermal patch – Vaginal ring – Injectables medroxyprogesterone – Implants etonogestrel – IUDs levonorgestrel or copper

What emergency contraceptive options exist?

Levonorgestrel Plan B within 72h – Ulipristal Ella within 5 days – Copper IUD within 5 days most effective

What are clinical indications for prescribing estrogen?

Contraception – Menopausal HRT – Female hypogonadism – Acne in young females – Gender transition therapy off-label

When is estrogen contraindicated?

Intact uterus if unopposed – ER positive breast cancer – Unexplained vaginal bleeding – History of DVT or PE – Stroke – MI due to clot – Cardiovascular disease or high risk smoker over 35 – uncontrolled HTN – First 21 days postpartum increased VTE risk

Which estrogen routes reduce clot risk compared to oral?

Transdermal forms – Spray – gel – patch – emulsion daily – Intravaginal cream or ring for local effects – Parenteral IV for acute heavy uterine bleeding only

Why are synthetic progestins used instead of natural progesterone?

Progesterone has rapid metabolism – Progestins are more stable

What progestin effects occur during menstrual cycle?

Drop in levels triggers menstruation – Stimulates breast epithelium growth – Causes depression and sleepiness – Raises body temperature at ovulation by about 1 degree F

What progestin effects occur during pregnancy?

Suppress uterine smooth muscle contractions maintain pregnancy – Suppress GI smooth muscle cause constipation – Promote alveolar tubule growth lactation prep

What are HRT risks and precautions?

Use lowest dose for shortest duration – Not for CVD prevention – Caution in women over 60 or more than 10 years past menopause

What are examples of SERMs?

Tamoxifen – Raloxifene – Ospemifene – Clomiphene

What are SERM indications?

Breast cancer prevention tamoxifen raloxifene – Osteoporosis raloxifene – Dyspareunia ospemifene – Infertility clomiphene

What are adverse effects of SERMs?

Hot flashes – Leg cramps – Risk of VTE – Tamoxifen increases risk of endometrial cancer

What is the main mechanism of estrogen in contraception?

Suppress FSH release – Stabilize endometrium

What is the main mechanism of progestin in contraception?

Suppress LH surge prevent ovulation – Thicken cervical mucus – Atrophy endometrium

What are benefits of combined oral contraceptives?

Cycle regulation – Less dysmenorrhea – Less acne – Decreased ovarian and endometrial cancer risk

What are adverse effects of combined oral contraceptives?

Nausea – Breast tenderness – Breakthrough bleeding – Increased risk of VTE – Stroke – MI – Especially in smokers over 35

What are contraindications for combined oral contraceptives?

History of VTE – Stroke – CAD – ER positive breast cancer – Migraines with aura – Smokers over 35 – Severe HTN – Active liver disease

What are non-oral hormonal contraceptive options?

Transdermal patch – Vaginal ring – Injectables medroxyprogesterone – Implants etonogestrel – IUDs levonorgestrel or copper

What emergency contraceptive options exist?

Levonorgestrel Plan B within 72h – Ulipristal Ella within 5 days – Copper IUD within 5 days most effective

Combined oral contraceptives prevent pregnancy by two main mechanisms — what are they?

Estrogen suppresses FSH release and stabilizes endometrium – Progestin suppresses LH surge prevents ovulation – Thickens cervical mucus – Atrophies endometrium

What benefits do combined oral contraceptives provide beyond pregnancy prevention?

Cycle regulation – Less dysmenorrhea – Less acne – Decreased ovarian cancer risk – Decreased endometrial cancer risk

What common adverse effects can occur with combined oral contraceptives?

Nausea – Breast tenderness – Breakthrough bleeding – Increased risk of VTE – Stroke – MI – Especially in smokers over 35

In which patients are combined oral contraceptives contraindicated?

History of VTE – Stroke – CAD – ER positive breast cancer – Migraines with aura – Smokers over 35 – Severe HTN – Active liver disease

Which non oral hormonal contraceptive methods are available?

Transdermal patch – Vaginal ring – Injectables medroxyprogesterone – Implants etonogestrel – IUDs levonorgestrel or copper

What unique issues exist with the contraceptive patch and vaginal ring?

Patch – Higher estrogen exposure and increased clot risk – Ring – Vaginal discharge and infection

The mini pill contains only one hormone — which one and what is its dosing limitation?

Progestin – Must be taken daily at the same time – Less effective than combined – Used when estrogen contraindicated

What contraceptive methods are considered long acting reversible contraception?

IUDs and implants – Highly effective – Long duration – First line recommendation

What side effects can occur with LARC devices?

Bleeding changes – Cramping – Expulsion risk – Rare perforation

What chemical in spermicides disrupts sperm membranes and what are its limitations?

Nonoxynol 9 – Must be applied before each act – Not very effective – May increase HIV risk

What is Phexxi and how does it prevent pregnancy?

Vaginal gel – Lactic acid – Citric acid – Potassium bitartrate – Maintains acidic pH – Inactivates sperm

Which EC pill is effective up to 72 hours by delaying ovulation?

Levonorgestrel Plan B – Best taken ASAP – Less effective in obesity – Available OTC

Which EC pill is effective up to 5 days and requires a prescription?

Ulipristal Ella – More effective closer to ovulation – Requires prescription – Less effective in obesity

What is the most effective form of emergency contraception?

Copper IUD – Can be inserted within 5 days – Not affected by obesity

Which drug used in medical abortion blocks progesterone receptors?

Mifepristone – Breaks down endometrium – Sensitizes uterus to misoprostol

Which drug used in medical abortion is a prostaglandin E1 analog?

Misoprostol – Induces uterine contractions – Expels pregnancy

What is the standard regimen for medical abortion up to 10 weeks?

Mifepristone 200 mg orally – Followed by misoprostol 800 mcg buccal 24–48 hours later

Which drug reduces heavy menstrual bleeding by blocking plasminogen activation?

Tranexamic acid – Antifibrinolytic – Reduces menstrual blood loss

Which SERM is used in infertility to block estrogen receptors in the hypothalamus?

Clomiphene – Blocks hypothalamic estrogen receptors – Increases GnRH – Increases FSH and LH – Stimulates ovulation

Which aromatase inhibitor is used in infertility to reduce estrogen levels?

Letrozole – Aromatase inhibitor – Lowers estrogen – Releases pituitary inhibition – Increases FSH and LH

How are gonadotropins used in infertility treatment?

FSH and LH injections – Directly stimulate ovaries – Used in assisted reproduction

Which medications are first line for nausea and vomiting in pregnancy?

Vitamin B6 pyridoxine – Doxylamine – Antihistamines

Which medications are second line for nausea and vomiting in pregnancy?

Ondansetron – Metoclopramide – Promethazine

Which drug prevents seizures in pre eclampsia and requires toxicity monitoring?

Magnesium sulfate – CNS depressant – Monitor for loss of reflexes – Monitor for respiratory depression

What physiologic changes in pregnancy alter drug pharmacokinetics?

Increased plasma volume – Increased renal clearance – Altered hepatic metabolism – Decreased albumin – Delayed gastric emptying

Which drugs are well known teratogens to avoid in pregnancy?

ACE inhibitors – ARBs – Warfarin – Isotretinoin – Valproate – Thalidomide – Methotrexate

What FDA rule replaced the pregnancy letter categories A through X?

PLLR rule – Provides narrative summary of risks – Includes clinical considerations – Includes data

Which drugs are contraindicated in breastfeeding due to risk to the infant?

Chemotherapy – Radioactive isotopes – Lithium – Amiodarone – Drugs of abuse

Which drugs are generally considered safe in breastfeeding?

Acetaminophen – Ibuprofen – Penicillins – Cephalosporins – Most antidepressants

Which medications are used to induce labor?

Oxytocin – Misoprostol – Dinoprostone

Which medications are used to treat postpartum hemorrhage?

Oxytocin – Misoprostol – Methylergonovine – Carboprost

Which anesthetic and analgesic options are used during labor?

Epidural local anesthetics plus opioid – IV opioids – Nitrous oxide