Lecture 5-6 Drugs for female reproductive health

Copper T (ParaGard) can be placed immediatley following

10 min following placenta delivery

•Emergency Contraceptive Pills (ECPs)-Ulpristal acetate (ELLA) is only effective in women up to

195 pounds, can be taken up to 5 days after

When can Plan B be used up until

3 days but is only effective up to 165 pounds therefore it has a shorter time frame and lower weight requirement than Ulpristal acetate (Ella)

What other drugs interact with flibanserin?

3A4 inhibitors, CNS depressants

A women is taking a combination estrogen-progestin oral contraceptive. She experiences a multitude of side effects. Which side effect is most likely due to what can be described as an 'progestin excess', and not likely due to the progestin content of the medication? A.Breast tenderness B.Vasomotor symptoms C.Menorrhagia D.Increased appetite Late cycle (day 15) breakthrough bleeding

INCREASED APPETITE

why are oral contraceptives considered a pregnancy category X?

because there is no need to take contraceptive when pregnant, NOT a problem with teratogenicity

Most of these drugs that induce 3A4 are what pregnancy category?

category C or D (or X) for pregnancy

What interaction occurs with BC and antibiotics?

change the gut microbiota that are responsible for enterohepatic re-cycling of estrogens and progestins—recommend back up method for duration of abx, especially if BTB no matter what you must warn patients to use back up methods when on oral bc and taking antibiotic

extended cycle regimens allow for

continuous hormones or has placebo pills only every 84 days

when taking prednisone and oral bc what happens?

decrease efficacy of OCC and increased prednisone ADRs

when taking valproic acid and oral bc what happens?

decrease valproate exposure resulting in increased risk of seizures!!!

cons of levonorgesterl IUD

higher number of bleeding days or spotting in first 3-6 months •No STI protection May cause ovarian cyst •Brief discomfort upon insertion or removal

Major adverse effect of drospirenone

hyperkalemia---d/t it's mineralocorticoid action

what is the serious AE associated with bremelanotide

hypertension •Limit to 1 dose in 24 hours; 8 doses per month due to development of hypertension

What are common AE of Medroxyprogesterone Acetate (MPA)(Depo Provera®)

injection site reaction Weight gain (6% SC, 37% IM) amenorrhea (up to 68%); similar to other progestin only

OC and Cervical cancer

jury's still out might increase might be related to HPV

New Drug Update: Phexxi®....what are the active ingredients?

lactic acid, citric acid, potassium bitartrate

Plan B one step is what formulation?

levonorgesterol

what are the common AE with nuvaring>

mood disorder vaginits vaginal discharge

what IUDs (long acting reversible contraceptive) are on the market??

non hormonal-copper-paraguard the rest are progestone only--levonorgesterl

high dose estrogen is preferred if a women is

obese steroids are highly lipophilic, therefore increased fat will allow for greater distribution and you will need a higher dose to be effective

OCs can reduce risk of

ovarian and endometrial cancers within 6 months of use also reduce risk of colorectal cancer

If someone is taking Drospirenone remember not to prescribe

potassium sparing diuretics, K+ supplements need to check potassium at baseline and monitor

what happens if the patch falls off and you notice in less than 24 hours

replace same or new patch immediately

Most antibiotics do not interfere with transdermal contraception...their is one exception, what is it?

rifamycins

MOA of Flibanserin?

serotonin 1A receptor agonist and 2A antagonist

Novel Progestin: Drospirenone is related to the drug

spironolactone

if your patch has fallen off and its been more than 48 hours

start a new 4 week cycle

How is a transdermal patch used

•1 patch q week for 3 weeks •Rotate application sites; apply to clean, dry skin •Do not cut or damage patch

What is a combined estrogen and progestin emergency contraceptive?

•2 doses (Yuzpe regimen: 1 dose of 0.1 mg of ethinyl estradiol plus 0.5 mg of levonorgestrel followed by a second dose of same 12 hours later) •Least effective, more frequent occurrence of side effects (N/V)

Bremelanotide (Vyleesi®)—MOA

•: melanocortin receptor agonist, MC1R and MC4R specifically (unknown as to why it works in HSDD)

what is specific about how you take progesterone only pills?

•Adherence is REQUIRED! •>3 hours = missed pill and opportunity for pregnancy •Use alarm clocks, smart phone apps, etc. •Back up method

What are some iatrogenic causes of low libido

•Antihypertensives (beta-blockers, diuretics) •Antidepressants, antipsychotics •? Contraceptives; specifically anti-androgenic progestins •Mixed data, conflicting studies

what should be avoided for 6 hours after taking flibanserin?

•Avoid activities requiring mental alertness or coordination for 6 hours after dose •If no efficacy after 8 weeks, discontinue common AE:nausea, dizziness, somnolence, fatigue

What BBW is associated with flibanserin?

•BBW: severe hypotension and syncope when used with EtOH (wait 2 hours+) •REMS program: inform patients about interaction with EtOH

Fertility Awareness Method (FAM) what are a couple of the methods people use?

•Calendar method •Cycle Beads® •Cervical Mucus •Basal Body Temperature

common AE of phexxi

•Common: Dysuria, UTIs, vaginal infections (bacterial, yeast), pruritus •Serious: cystitis, pyelonephritis

What are complications that occur with nexplanon

•Complication of insertion may arise: migration of implant, infection •Common: pharyngitis (10.5%), URI (12.6%), implant site reaction up to 9.6%, otherwise similar to progestin only •Serious: similar to progestin-only, mainly CVD or VTE

what are the serious AE of bc?

thromboembolic disease, MI, CVA, HTN

what are the serious AE of the nuvaring?

vaginal ulcer, impaired fasting glucose, otherwise similar to other hormonal contraception

Lactational Amenorrhea Method (LAM)

•Contingent upon exclusive or nearly exclusive breastfeeding •Surge in prolactin from nursing, inhibits ovulation; also may inhibit implantation •Both day and night feedings •Amenorrhea present (does not include postpartum spotting) •Infant is less than 6 months old

Novel Progestin: Drospirenone MOA

•Decrease free testosterone (less androgenic than other progestins) •Anti-mineralocorticoid action (derived from spironolactone)

Female Sexual Dysfunction: Hypoactive Sexual Desire Disorder (HSDD) is associated with (not caused by)

•Diabetes, metabolic syndrome, obesity •Menopause, postpartum

when should a transdermal patch not be used 1st line?

•Efficacy is lower in women weighing >90 kg; should not be first line

what are the names of synthetic estrogens?---she said to know estrogen vs progestin

•Ethinyl estradiol (EE) •Mestranol (metabolized to EE) •Estradiol valerate

What two meds are on the market for low libido in women?

•Flibanserin (Addyi®)—Oral drug taken every night at bedtime •Bremelanotide (Vyleesi®)—On demand SC injection, 45 minutes before sexual activity

What drugs are oral bc contraindicated with?

•HIV/hepatitis C protease inhibitors—may increase chances of liver injury •Tranexamic acid (increased risk of VTE)

trandermal patches are contraindicated

•Heat sources on or near patch •Skin integrity

The benefits of Drospirenone

•Help decrease hormone-related acne •Decreases epithelial DNA synthesis in endometrial tissue •Help decrease symptoms of pre-menstrual dysphoric disorder (PMDD) •Bloating, acne

if someone is taking a 3A4 inducer what can be done?

•Higher dose estrogen for CPCs (50 mcg EE), Barrier form of contraception, IUD •Supplement with folic acid 0.4-0.8 mg/day (up to 4 mg/day recommended in seizure disorder patients)

what about intercourse and the nuvaring??

•Keep in place for intercourse (if bothersome to patient or partner, can remove for <3 hours)

what are the names of progestins

•Levonorgestrel •Norethindrone (acetate) •Norgestrel •Ethynodiol diacetate •Norgestimate •Dienogest •Norethynodrel •Desogestrel •Gestodene •Drospirenone

MOA of phexxi

•MOA: lowers pH of vagina to reduce sperm motility •NON-HORMONAL!! •Intravaginal insert, use before or up to 1 hour after vaginal intercourse

what are some benefits of extended cycle aka continuously taking oral bc

•Maintain consistency of taking pill daily •Manipulation of timing and frequency of menses-•Avoid menses for events (vacation, honeymoon, athletic events, etc) •Decrease symptoms of premenstrual syndrome or premenstrual dysphoric disorder (PMS or PMDD) •Decrease menses and symptoms associated with problematic menses (blood loss, anemia, cramps/pain) •Regulates menses to a more predictable schedule

Pros of a levonorgesterl IUD

•May decrease blood loss up to 70% at one year •Amenorrhea may develop in some patients •Once placed, very little maintenance (check strings, etc)

can women who are breast feeding or pregnant take bremelanotide?

•Not recommended for pregnant or breastfeeding women

What are the main pharm options for birth control?

•Oral Tablets •Intra-Uterine Devices (IUDs) •Transdermal Patches •Implants/Injections •Intra-Vaginal Ring

An otherwise healthy 25 year old nulliparous woman has just been diagnosed with a lower extremity deep venous thrombus (DVT) after orthopedic surgery. She has been placed on therapeutic anticoagulation for treatment. Up until this point, she had been taking a combined oral contraceptive pill. She presents to her gynecologist for contraceptive counseling. The best next step is: A.Discontinuation of combined oral contraceptive until anticoagulation therapy is complete B.Transition to an oral contraceptive pill containing a lower dose of estrogen C.Transition to levonorgestrel IUD D.Transition to copper IUD E.Continue current combined oral contraceptive

(C) Transition to levonorgestrel IUD. i guess copper isn't first line because it is can increase bleeding

Your patient, who is taking an oral contraceptive, has heard about and asks about the risk of thromboembolism as a result of taking these drugs. To reduce the risk of this potentially severe adverse hematologic response, but still provide reasonably effective contraception, what would you prescribe? A.A combination product with a higher estrogen dose B.A combination product with a higher progestin dose C.A combination product with a lower estrogen dose D.A combination product with a lower progestin dose E.A product that contains only estrogen

A combination product with a lower estrogen dose estrogen=what is the main cause of the clotting

Which of the following patients is the best candidate for combined oral contraceptives? A. 45-year-old with a family history of breast cancer B. 37-year-old smoker C. 32-year-old with a history of a pulmonary embolism during her most recent pregnancy D. 25-year-old with a history of migraines with aura 38-year old with hepatocellular carcinoma

A-family hx of breast cancer seems odd but I guess if you dont have the cancer it's just a family hx it's okay

A woman has been sexually assaulted and she wishes to have her pregnancy terminated by pharmacologic means. What is generally the most appropriate drug? A.Levonorgestrel B.Methotrexate C.Mifepristone D.Ulipristal E.Copper IUD

A.Levonorgestrel B.Methotrexate C.Mifepristone D.Ulipristal E.Copper IUD Progesterone antagonist: not the same as emergency contraception. Once the zygote has been implanted, EC is not effective (hence the decreasing efficacy with increasing time after unprotected intercourse)

Which of the following would be indications for seeking medical care after taking emergency contraception? A. Menses over two weeks late B. Abdominal pain C. Irregular bleeding D. All of the above E. None of the above

ALL OF THE ABOVE

Oral Contraceptive Danger Signs...points to counsel on when to see medical attention

Abdominal Pain (VTE of abd or pelvis?) Chest Pain or Cough (PE?) Headaches—severe (stroke, migraines?) Eye Problems—complete or partial loss of vision (stroke?) Severe Leg Pain—calf or thigh (DVT?)

Your patient is a 38-year-old G2P2 female with type 2 diabetes mellitus for 2 years that is controlled with metformin. She presents for her annual gyn exam and request a prescription for oral contraceptive pills. She smokes heavily quoting around 2 packs per day. Her family history is significant for CVA (mother). When you are deciding to prescribe an oral contraceptive to this patient, which of the following will prompt serious consideration of whether or not to recommend another method of contraception? A.Parity B.Smoking C.Physical Activity D.Diabetes Serum HDL

B-smoking, more than 15 a day

A 23 year old nulliparous patient presents for contraceptive counseling. She is about to start medical school and does not plan on getting pregnant for many years. Her past medical history is notable for epilepsy, first diagnosed as a child. She has been on various medications to control her symptoms over the years but has been well controlled on carbamazepine for the last two years. You review the failure rate of oral contraceptives, depo medroxyprogesterone acetate (DMPA), and intrauterine device (IUD) contraception among the general population. She prefers oral contraception. Given her history of epilepsy you recommend intrauterine device contraception because: A. The metabolic interaction between antiepileptic and oral contraception is harmful to the liver B. The metabolic interaction between antiepileptic and oral contraception reduces the effectiveness of the OC C. The metabolic interaction between antiepileptic and oral contraception results in increased seizure activity D. Epileptic patients are a higher risk of stroke when taking estrogen E. Epileptic patients are at higher risk of clot when taking estrogen

B. The metabolic interaction between antiepileptic and oral contraception reduces the effectiveness of the OC

Drugs that induce 3A4 lower the concentration of the birth control=less effective, what are some drugs that induce 3A4?

Barbiturates carbamazepine topiramate corticosteroids griseofulvin phenytoin pioglitazone modafinil armodafinil, rifampin, and rifabutin, etc. induce 3A4 (i.e., metabolize estrogens and progestins quicker)

A women who has been taking an oral combined contraceptive pill for several years is diagnosed with epilepsy and started on phenytoin. What is the most likely consequence of adding phenytoin? A.Breakthrough seizures from increased phenytoin clearance B.Phenytoin toxicity C.Reduced contraceptive efficacy D.Thromboembolism from the estrogen component of the contraceptive E.Thromboembolism from the progestin component of the contraceptive

C.Reduced contraceptive efficacy

Drospirenone has a BBW, what is it?

Cigarette smoking increases the risk of serious cardiovascular events from oral contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Women who are over 35 years of age and smoke should not use oral contraceptives

A 25 year old woman has just undergone Roux-en-Y gastric bypass surgery and presents to your clinic requesting contraception. Medical history is negative for hypertension and headache, and notable only for acne and irregular vaginal bleeding secondary to known submucosal uterine fibroids. She is mutually monogamous with one male partner. The BEST contraceptive method for this patient is: A.Combination oral contraceptive pill B. Progestin-only contraceptive pill C. Copper IUD D. Etonogestrel subdermal implant E. Levonorgestrel IUD

Correct answer: (D) Etonogestrel subdermal implant. Oral contraceptives should be avoided in women who have had malabsorptive bariatric surgeries. IUDs may be at higher risk for expulsion in women who have uterine cavities distorted by submucosal fibroids.

A 27-year-old G0 with a copper intrauterine device (IUD) placed 2 years ago presents to the emergency room with severe pelvic pain, fever, nausea, and vomiting. An ultrasound demonstrates fundal placement of the IUD, with normal adnexae. She is diagnosed with pelvic inflammatory disease (PID), and the plan is to admit her for IV antibiotics. How should the IUD be managed? A. The IUD should be removed immediately after the diagnosis of PID is made B. The IUD should be removed after her first dose of IV antibiotics to reduce the patient's risk of bacteremia C. The IUD can be left in place until she has defervesced, then it should be removed D. The IUD can be left in place with consideration of removal only if she does not respond to antibiotics

Correct answer: (D) The IUD can be left in place with consideration of removal only if she does not respond to antibiotics. Explanation: The risk of PID with an IUD in place is quite small. Treatment of PID does not require IUD removal, and routine antibiotics should be administered in this case. If 48-72 hours pass without clinical improvement, IUD removal can be considered, but it has not been shown to improve outcomes in that setting.

A women wants a prescription for an oral contraceptive, and your choice is between an estrogen-progestin combination and a 'minipill'(progestin only). Compared with a hormone combination product, what is the main difference that would occur when a progestin-only approach is used? A.Better contraceptive efficacy B.Direct spermicidal effects C.Higher risk of thromboembolism D.More menstrual irregularities E.Poorer compliance due to taking the drug on an irregular cycle, rather than daily

D.More menstrual irregularities

how would you manage estrogen excess

Decrease estrogen content, consider progestin only or IUD quick cycle aka continous regimen NSAIDS for dysmenorrhea

How do you treat progestin excess??

Decrease progestin content choose less androgenic progestin

A 37-year-old female is interested in oral contraception. She is newly married and sexually active with her husband. She has 2 children from a previous relationship and does not desire any children. She drinks alcohol intermittently, likes rock climbing and smokes 1 pack of cigarettes per day. This patient is at risk for which of the following complications if she starts combined oral contraceptives? A.Hypertension B.Endometrial carcinoma C.Trichomoniasis D.Unwanted pregnancy E.Deep Venous Thrombosis

Deep Venous Thrombosis

Progestin Deficiency adverse effects

Dysmenorrhea, menorrhagia (progesterone antagonizes estrogen so sx here are related to excess estrogen action) Late cycle (days 10-21) breakthrough bleeding or spotting

According to the CDC Medical Eligibility Criteria for Contraceptive Use, which of the following contraceptive methods is contraindicated in women with a history of ovarian cancer (not actively undergoing treatment)? A.Depot medroxyprogesterone acetate injection B. Etonogestrel subdermal implant C. Copper IUD D. Levonorgestrel IUD E. None of the above

E. None of the above also strange, I feel like if someone has a hx I am probably not gonna mess with hormones but for this test know it's okay

How can you manage estrogen deficiency?

Exclude pregnancy increase estrogen content or continue current if amenorrhea is acceptable

At her first gyn visit a 22 year old woman asks for birth control pills. Her cycle is regular, every 28-31 days, she has a heavy flow, lasting for about 5 days. Her mother has a history of deep venous thrombosis. You recommend prior to starting oral contraceptives she have which of the following tests? A. Cervical cytology screening B. Factor V Leiden Testing C. Pelvic ultrasound D. TSH E. Endometrial biopsy

Factor V Leiden Testing

Combined Oral Contraceptives (Birth Control Pills with both Estrogen and Progestin) the dosing can be

Fixed or phasic •Fixed dose estrogen-progestin: monophasic •One strength of progesterone and estrogen for the entire cycle •Chewable, + Folate and + Fe options available •Phasic estrogen-progestin •Biphasic, Triphasic and Multiphasic (different combinations of strengths) •Estrophasic: Progestin content remains the same; Fe option available

when would a birth control overdose need to be considered?

If the patient is taking one with an iron supplement! there is no significant toxicity in oral contraceptives unless Fe containing

when should a copper IUD not be used

If you want to keep a pregnancy-otherwise can cause abortion Abnormal uterine anatomy Abnormal bleeding of unknown etiology (relative, until diagnosed/corrected •Current STI or PID (until treated) •Uterine/cervical cancer (ok to leave in place?) •Copper allergy

How do you manage progestin deficiency?

Increase progestin content, consider extended-cycle or continuous regimen, consider progestin-only or IUD, NSAIDs for dysmenorrhea

what are the adverse effects of excess progestins

Increased appetite, weight gain, bloating, constipation, depression, fatigue, irritability Acne, oily skin, hirsutism

cons of paragard IUD

Increased menstrual blood loss (up to 50% more); NSAIDs can help Increased dysmenorrhea No STI protection (like everything when a condom isnt used)

•Intramuscular or subcutaneous injection, received q3 months...what drug is this?

Medroxyprogesterone Acetate (MPA)(Depo Provera®) note: progestin only

Adverse effects of estrogen excess

Nausea, breast tenderness, headaches, cyclic weight gain due to fluid retention Dysmenorrhea, menorrhagia, uterine fibroid growth

Pregnancy test prior to emergency contraceptive use, is it required?

Nope, it's optional

Intravaginal Contraception

Nuva ring: Ethinyl Estradiol/Etonogestrel, continuous delivery (no spike in concentrations like OCs) estrogen + progestin

Transdermal Patches

Ortho Evra® (or generic Xulane®) •Transdermal delivery system for combined hormonal contraception •EE 35 mcg + norelgestromin 150 mcg/day contained in patch adhesive

What are the adverse effects of estrogen deficiency

Vasomotor symptoms, nervousness, decreased libido, early cycle (days 1-9) break through bleeding or spotting Absence of withdrawal bleeding (amenorrhea)

what disease would you not want to use a copper IUD in?

Wilson's disease!

does transdermal contraception have the same contraindication as combined oral?

YES •Same contraindications and precautions apply as combined oral contraceptives (hormonal) •same as OCs (no smoking >35 years of age due to risk of serious cardiovascular AEs)

Do intravaginal etrogen+progestin have the same contraindication as as other estrogen/progestin containing drugs

YES •BBW: women over 35 should not smoke... same

Combines oral contraceptives are prescribed for the obvious reason of birth control but what are some other common reasons that people use oral contraceptives

acne, dysmenorrhea, menorrhagia, iron-deficiency anemia, peri-menopausal symptoms

what drug drug interaction is noted with nuvaring?

alprazolam... otherwise similar to IUD

what is the patch falls off but you dont notice for >24 but <48 hours

depends on the week, usually use back-up method x1 week •Day 22-28 just leave it off and start new cycle when it's time

In addition to being used for daily contraception prevention, paragard can be used for

emergency contraception paced within 5 days

MOA of combined oral contraceptives

•Prevents ovulation by Suppressing the follicle-stimulating hormone-luteinizing hormone (FSH-LH) sequence from the anterior pituitary •Estrogens: suppresses FSH and inhibits the maturation of dominant follicle •Progestins: suppresses LH surge, inhibits endometrial proliferation and thickens cervical mucus

What are the major counseling points when prescribing oral BC

•Starting •1st day of menses start...or...Sunday after menses start •Take a pill every day (may not be acceptable to some women...) •Pair with another activity done daily (e.g., brushing teeth) or use cell phone app or alarm for reminder •Missed dose instructions •Catch up (i.e., take 2 pills in one day if required), do not skip doses! •Use back-up contraception (or abstinence) for 7 days if >2 doses missed •Break-through bleeding and other side effects •Common in first 3-6 months after starting; continue OCC as prescribed, if tolerable •Will likely subside, if not, can switch at 3 months (or sooner if intolerable)

instruction for starting Ethinyl Estradiol/Etonogestrel intravaginal

•Use back up method for 7 days if no or other contraception was used in the last month (except for OCs) •Starting: insert new ring on 1st day of menstrual period but can be started at anytime during cycle (may result in menstrual irregularities for first few months) •Keep ring in for 3 weeks and remove for 4th week in cycle for w/d bleeding Can leave in place for 4 weeks (30-31 days) to achieve extended cycle but use is off-label

YOU ABSOLUTELY MUST FO SHO KNOW the contraindication of combined oral contraceptives

•VTE disease, CVA, uncontrolled hypertension (>160/>100 mmHg) •Hormone dependent cancers † •Migraine with aura † •Migraine without aura >35 y.o. •>35 y.o. and smoking >15 cig/day •Liver tumors †, decompensated cirrhosis †, acute or flare of viral hepatitis

levonorgesterl IUD are contraindicated in patients with a hx of

•active liver disease uterine abnormality (structural, functional, infectious, bleeding of unknown etiology, etc) current or history of cancer

What is a serious side effect of Medroxyprogesterone Acetate (MPA)(Depo Provera®)?

•anaphylaxis, decreased bone mineral density (BMD) (osteopenia/porosis) and fracture of bones with prolonged use •Calcium/vitamin D and weight bearing exercise to help mitigate decrease in BMD

Estrogens and progestins are metabolized by

•cytochrome P450 enzyme 3A4

implantable birth control (Etonogestrel Implant) is placed

•in the medial, proximal portion of the non-dominant arm •Replace "no later than 3 years" PROGESTERIN only BC

MOA of the copper IUD

•inhibits sperm motility; sterile inflammatory reaction in endometrium leads to phagocytosis of the sperm

Use EC as an opportunity to discuss

•more reliable contraception •Copper T is good for 10-12 years once placed

Bremelanotide cannot be taken with

•naltrexone (treatment failure)

if you take sugammadex and oral bc what happens?

•progestin binding

•For oral dosage forms: vomiting within <3 hours of dose what do you do?

•re-dose ASAP •May consider pre-treatment with antiemetics 1 hour prior to ECP (e.g., ondansetron, promethazine)

what do you do if the ring falls out?

•rinse with cold or lukewarm water and re-insert •If out for >3 hours, use back up method for 7 days

Progesterone Only Pills (Mini Pill) is indicated for use in

•women whom cannot take or risk > benefit of an estrogen containing drug Recommended in breastfeeding