Women's Health - PHARM

Ovaries produce estrogen.

What is its most active form?

estradiol

which form of E has an incr risk of VTE when taken at high doses?

ethinyl estradiol

What converts androgens into estrogen?

aromatase

menopausal sx’s are the result from a decr. in E:

What are some examples of vasomotor, bone effects, lipid effects, cognitive effects from that decr.?

Vasomotor symptoms:

• hot flashes

• night sweats

• sleep dx

• Urge incontinence + incr. frequency

• UTIs

• dryness

• dyspareunia

• Female sexual arousal disorder

• Osteoporitic bone loss

• Altered lipids: incr LDL / decr HDL

• difficulty problem-solving / short-term memory loss

What is the physiological effect of E (vasomotor, bone effects, lipid effects, cognitive effects)?

• ductal growth in breast

• vaginal + uterine epithelium growth

• blocks bone resporbtion

• decr. vasoconstriction 

• incr. perfusion

• decr. LDL / incr. HDL

• preserves cognitive fct

• regulates mood

What are key ADE of estrogen therapy?

• Endometrial hyperplasia // Endometrial cancer (if unopposed E)

• Thromboembolic risk

• N / V (improves with use)

• breast tenderness

• HA (migraines)

• Fluid retention (bloating / edema) → inc. BP 

• hepatic effects (gallbladder dx, adenomas, etc.)

T/F: A pt. taking birth control that includes E in the formula could experience N, breast tenderness, and edema.

TRUE. E imbalance

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?

• intact uterus (if unopposed E)

• ER (+) breast cancer / unexplained vaginal bleeding

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

• pregnancy

• active liver dx

Which estrogen routes reduce clot risk compared to PO?

Transdermal form (spray / gel / patch / emulsion)

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) have “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 (tx and decr. risk of breast CA) // agonist in bone (protects against osteoporosis) & endometrium

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?

rapidly 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 from E) 

• Contraception

• Supporting early pregnancy

What are ADE of progestins?

• HA

• irreg. bleeding (esp if P-only tx)

• Depression

• Weight gain / bloating

• Libido changes / fatigue

• Breast tenderness

• decr. HDL / incr. LDL (older agents)

• incr breast cancer risk (when combined with E)

T/F: A pt. taking birth control that includes P in the formula could experience incr. appetite, fatigue, and depression.

TRUE. P imbalance

What are C/I for progestins?

• Unexplained vaginal bleeding

• Active liver disease / tumors

• breast cancer (or other hormone-sensitive)

• preg.

What are forms of progestin?

• PO

• IM

• SQ

• Intravaginal

• Transdermal

Indications for HRT? What are alt. to HRT?

• low dose sys. → tx sx of menopause (GU + vasomotor)

  • alt: SSRI / SNRI / clonidine

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

  • not 1st line!

Which HRT regimens are used considering uterus status?

• Intact: Estrogen + progestin

• Absent: Estrogen only

USPSTF says HRT can reduce risks like…

• menopausal sx (vasomotor + GU + osteroporosis)

• DM

• Colon Cx

• CHD in those < 60 y/o

USPSTF says HRT can increase risks like…

• thromboembolism

• CHD in those > 60 y/o

• gallbladder dx

• E+P forms: breast cancer // dementia

• urinary incontinence

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 → lowest dose + short-term

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?

fezolinetant = 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] while [P] remains the same

What meds are used in transgender women therapy?

• Estrogen

• Anti-androgens (ex. spironolactone)

What meds are used in transgender men therapy?

Testosterone

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

Filbanserin // Bremelanotide

What is flibanserin’s indications for females?

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

• qd x several wks to see benefits

  • D/C if ≠ improvement after 8 wks

Why is Filbanserin Rx through a REMS program?

• hypoTN and syncope

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

What is bremelanotide’s MOA, PK, C/I?

• Melanocortin receptor agonist

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

• C/I: unctrl HTN / CVD dx

In what ways can contraceptions prev preg?

• prev. implantation into endometrium

• prev fertilization

T/F: in studies, implants are more effective than vasectomy

TRUE!

T/F: adherence is a significant determining factors for contraception efficacy. the ones that require less adherence (less need to be proactive), are more effective

TRUE. ex. having to remember to take take pills qd at relative same time

What is the main mechanism of estrogen in contraception?

Suppression of FSH → no follicle maturation

also good at regulating bleeding since no ovulation, no start of menses

T/F” in birth control, progesterone is more important than estrogen

TRUE

What is the main mechanism of progestin in contraception?

prev LH surge → no ovulation → Thickens cervical mucus → no implantation

T/F: placebo pills allow for menstruation

TRUE

What are the ADE of E in contraceptives?

• inc risk of VTE → use P-only but s/e = irreg. bleeding

• incr BP

T/F: Progestin has no VTE risk!

TRUE

T/F: for combo OCPs, the starting dose is 50 micrograms.

FALSE. now 20-35 mcg

What is the typical PK / admin for combo OCP

28 days worth of pills: 21 of active hormones + 7 days placebo

T/F: monophasic combo OCPs are the most common and is a constant dose of E+P

TRUE.

T/F: biphasic combo OCPs have 3 different doses of hormones

FALSE. triphasic does

Continuous combo OCPs involves NO menstruation = 7 additional days of hormone exposure, what risk is indicated?

very low risk of endometrial hyperplasia

T/F: extended-cycle combo OCPs means menstruation q3mos

TRUE

When starting combo OCPs, what initiation date offers immediate protection

1st day of menstrual cycle ≈ 14 days of hormone build-up until expected next ovulation

Combo OCPs can also be initiated the next Sunday after menses for easy tracking, what additional intervention is needed?

back up contraception x 7 days

Which contraceptive method has more E (incr risk of VTE) than the combo OCP? What is its PK? 

Transdermal patch are initiated on the 1st day of menstruation → changed weekly x 3 → none on 4th week for menstruation

• if 24+ hrs w/o → start new cycle + back-up x 7 days

Vaginal contraceptive rings are inserted monthly → stays for 3 wks + removed for 1 wk, what scenarios require a back up method?

3+ hrs w/o ring → replace ring + back-up x 7 days

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

• Progestin (less risk of thromboembolism, HA, N, etc.) → irreg bleeding

• qd (continuous or 24 days active hormone + 4 days placebo)

• less effective than combo OCPs

• back-up required for 2 days if forgot a dose

What is the initiation schedule of the mini pill?

1st day of menses + back-up x 7 days

T/F: the O-pill is OTC

TRUE

What contraceptive methods are considered long acting reversible contraception (LARC) and what is the 1 hormone it releases?

• IUDs // implants // depot inj

• progestin only → irred. bleeding

• ± used immediately post-partum (safer!)

what is the main component in the subdermal implant LARC? What is the PK efficacy and S/E?

• etonogestrel

• placed btwn biceps & triceps → protects for 3 yrs → gone w/n 5-7 days after d/c

What is the main component in the Depot inj LARC? What is the PK, pt edu, and BBW?

• medroxyprogesterone acetate

• IM / SQ inj q13 wk

• pt. edu: infertility for ≈9 mos after d/c

• BBW: osteoporosis

  • USPSTF (<2 yrs) vs ACOG (2+ yrs) about duration of use

What is the position of the following organizations for the usage of Depot > 2yrs?: FDA vs ACOG

• FDA “BBW” recs. no more than 2 yrs of use d/t risk of osteoporosis while ON it

• ACOG: benefits are greater than risks + s/e are reversible → use > 2 yrs

What are the 2 different LARC IUDs? What is the PK efficacy and S/E?

• levonorgestel (protects for 3-7 yrs) vs non-hormonal copper (protects for 10 yrs)

• S/E: cramping d/t insertion

What spermicidal chemical disrupts sperm membranes and what are its limitations (PK and S/E)?

• Nonoxynol (chemical surfactant) — foam, gel, jelly, suppository, vaginal film, sponge

• Must be applied no earlier than 1hr before intercourse

• minimal S/E: may incr. risk of HIV d/t lesion-forming promotion

What is Phexxi (contains Lactic acid, Citric acid, & potassium bitartrate) and how does its MOA prevent pregnancy?

vaginal gel applied 1hr before intercourse → pH modulator → inhospitable environment for sperm

T/F: the primary reason for contraceptive failure is d/t non-adherence

TRUE

why can you not find OCPs (esp combo) OTC?

incr. risk of thrombosis

Which EMR contraception pill tries to delay ovulation → ≠ fertilization if w/n 72 hrs (possibly even by day 5)?

Levonorgestrel (Plan B — OTC) = progestin-only

*≠ effective if fertilization has happened + does not affect implantation!*

Which EMR contraception pill is suppresses ovulation (effective up to 5 days) and requires a Rx?

Ulipristal acetate (Ella)

how many doses of combo OCP can be used as EMR contraception to prev. ovulation / fertilization / implantation

2 doses w/n 3 days after intercourse

what Rx is highly effective for prev. ovulation + terminating pregnancy but not actually approved as EMR contraception?

What is its MOA? Legality status in texas?

mifepristone → blocks progesterone

Illegal to use for abortion on viable preg.

What is the EMR contraception that imparies sperm fct and implantation as long as it is inserted w/n 5 days?

Copper IUD

Which drug combo is used to induce a medical abortion?

mifepristone → misoprostol

what is the MOA of mifepristone for abortive indications?

blocks progesterone receptor → detachment + cervical dilation + incr. prostaglandin production (induces contractions)

what is the MOA, ADE, and C/I of misoprostol for abortive indications?

synthetic prostaglandin → reinforces uterine contractions + helps expel remains of conception

• ADE: abd pain / vaginal bleeding / N + V / D / HA / infxn

• C/I: ectopic pregnancy / hemorrhagic dx / usage of anti-coag rx

Methotrexate (inhibits DNA synethesis) can be used as an abortive medication, but typically indicated for what specific dx?

ectopic pregnancies

PCOS is mostly sx mgmt of acne, irreg. menses, hyperglycemia, infertility, and larger habitus. What are some options?

• lifestyle: WL, diet

• combo OCPs or spironolactone

• insulin resistance: metformin

• infertility: letrozole

• Which SERM is used in infertility to makes E levels look low (competes w/ E) → incr. FSH → stimulation of follicle development → induces ovulation?

*associated w/ multiple gestations*

• PK for when to take Rx? When to D/C?

• ADE? C/I?

Clomiphene — taken qd x 5 starting the 5th day of menses

• D/C after 3rd attempt

• S/E: decr visual acuity / flushing

• C/I: pregnancy / AUB / liver dx / ovarian cysts

Which Rx reduces estrogen levels (inhibits aromatase)→ incr. FSH → follicular stimulation → ovulation induction?

*associated w/ multiple gestations*

• PK for when to take Rx?

• ADE? C/I?

Letrozole – start on 3rd day of menses for qd x 5 days

• S/E: edema / sweating / hypercholesterolemia / fatigue

• C/I: pregnancy

what infertility tx is an exogenous gonadotropin (mainly FSH) that stimulates follicular development?

*associated w/ multiple gestations*

• PK? ADE?

leuprolide — IM / SQ inj (2nd-line)

ADE: ovarian hyperstimulation syndrome

T/F: during flu szn, preg pt are rec to get the flu, RSV, and COVID (per current guidelines) with no required criteria met

FALSE. RSV only during Sep-Jan IF 32-36 wks

What other NON-live vaccines aside from the ones for viral colds can be considered for preg pt

tdap (27-36 wks GA)

Hep A/B 

meningococca

What is the general mgmt for N/V in preg. pt

stay hydrated + small meals + meds

Which medications are 1st and 2nd line for N / V in pregnancy?

1st line = pyridoxine (vit B6) ± Doxylamine

2nd-line = ondansetron, promethazine

Pre-eclampsia = HTN >160/110 after 20wks GA, what anti-HTN meds are preg safe

labetalol

nifedipine

methyldopa

Which Rx prevents seizures in eclampsia

Magnesium sulfate

What Rx promotes fetal lung development?

steroids

T/F: most drugs have yet to be tested for use during pregnancy

TRUE. risks are unknown d/t lack of data

What are the 3 criterias for Rx to be classified as teratogenic?

• cause characteristic malformation

• MOA during a specific window of vulnerability

• incr. dosage / duration of exposure → incr. incidence of malformation 

T/F: teratogenic effect depends on the developmental stage (pre-implantation / embryonic / fetal) of conception

TRUE

• pre-implantation (up to 2 wks) = all or nothing

• embryonic (wks 3-8) = gross malformations

• fetal (wk 9-term) = disruption of fct

use the mnemonic TERATO-JENS to list drugs are well known teratogens to avoid in pregnancy?

• Thalidomide

• Epileptic drugs (valproic acid)

• Retinoids

• Abx (quinolones / tetracyclines) + ACEi / ARBs

• Third element (lithium)

• Oral contraceptives / hormones

• Jantoven (warfarin)

• Ergotamines (dihydroergotamie)

• NSAIDs

• Statins

Since the FDA recently phased out the old classification of drug effects during pregnancy, we should still understand the old system.

Explain the A-X letter classification.

A-C = slight to greater risk

D & X = harms fetus

T/F: a lot of meds can enter breast milk, making it a significant factor to consider

FALSE

Which medications are used to induce labor?

Oxytocin // misoprostol

what med is given as a regional anesthetic in an epidural or spinal

bupivacaine