14-loflin-pharmacologic methods of contraception...hormonal contraception can worsen or cause...

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� Explain the physiology of the normal menstrual cycle and the role contraceptives play in preventing pregnancy

� Discuss methods of contraception and their pharmacologic properties

� Identify patient populations that require special considerations

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� Median length is 28 days, but can last from 21 to 40 days

� Begins with menarche, usually around 12 years of age, and ends with menopause, usually around 50 years of age

� Comprised of three phases: follicular phase, ovulation, and luteal phase

Shrader SP, Ragucci KR., Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014

Menses begins

Follicle Stimulating Hormone

(FSH) levels rise

One dominant follicle

secretes estradiol,

progesterone, and androgen

Menses is stopped

The endometrial lining of the

uterus is thickened and thin, watery

cervical mucus is

produced


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Mid-menstrual cycle the

anterior pituitary releases a surge

of luteinizing hormone (LH)

and the follicle releases a surge

of estrogen

This triggers follicular rupture and the release

of an oocyte

The oocyte then travels to the

fallopian tube to be fertilized and

the uterus for implantation


Non-dominant follicles form the corpus

luteum, which synthesizes estrogen,

progesterone, and androgen

Corpus luteum degenerates

and progesterone

declines

Progesterone

maintains the

endometrial

lining for the

embryo

Endometrial shedding

occurs and menstrual

cycle starts over

Human

chorionic

gonadotropin

(HCG)

stimulates

progesterone

and estrogen

production


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� Ethinyl estradiol

� Stabilizes endometrial lining and provides cycle control

� Contraceptive mechanism

› Suppress FSH release, which may prevent LH surge and subsequently prevent ovulation


� First generation: norethindrone, norethindrone acetate

� Second generation: levonorgestrel and norgestrel

� Third generation: norgestimate� Fourth generation: drospirenone� Provide most of the contraceptive effect� Contraceptive mechanism› Thicken cervical mucus to prevent sperm

penetration and slow motility

› Enhance endometrial atrophy

› Block LH surge and subsequently prevent ovulation

Shrader SP, Ragucci KR., Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014PL Detail-Document, Hormonal Contraception. Pharmacist’s Letter/Prescriber’s Letter. March 2013.

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� Low-Dose vs. High-Dose

› Refers to the dose of ethinyl estradiol (EE)

› Doses range from 10 mcg/day to 35

mcg/day

� “-phasic” (ex: mono-, bi-, tri-, four-)

› Refers to the number of different doses of

estrogen, progesterone, or both

› For example: triphasic Ortho Tri-Cyclen®

contains EE 35 mcg and norgestimate 0.18

mg x 7d, 0.215 mg x 7d, and 0.25 mg x 7d

� Extended-Cycle› Most provide active pills for 84 days

› Followed by either 7 days with low-dose estrogen or 7 days pill-free

� Continuous-Cycle› Continuous active pills

› Amethyst® is the only product available in the U.S.

� Can mimic these regimens with monophasic oral contraceptives

Clinical Resource, Comparison of Oral Contraceptives and Non-Oral Alternatives. Pharmacist’s Letter/Prescriber’s Letter. February 2018.

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� A good starting place for most women is a product with 20 mcg EE and levonorgestrel/norethindrone

� Back-up contraception is needed for 7 days after initiation

� Consider coexisting medical conditions and risk factors when selecting a product


Adverse Effect Likely Cause Response

Nausea, breast tenderness,

increased blood pressure,

melasma, headache

Too much estrogen Decrease estrogen content

Early or mid-cycle

breakthrough bleeding,

increased spotting,

hypomenorrhea

Too little estrogenIncrease estrogen content,

switch progestins

Breast tenderness, headache,

fatigue, changes in moodToo much progestin Decrease progestin content

Late breakthrough bleeding Too little progestin Increase progestin content

Increased appetite, weight

gain, acne, oily skin, hirsutism,

increased LDL, decreased HDL

Too much androgenSwitch to a third or fourth

generation progestin

Local irritationTransdermal patch or vaginal

ring useSwitch to an oral dosage form

PL Detail-Document, Hormonal Contraception. Pharmacist’s Letter/Prescriber’s Letter. March 2013.

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� Late dose = < 24 hours past intended administration

� Missed dose = ≥ 24 hours past intended administration

� Could increase adherence with use of the patch or vaginal ring

Curtis KM, et al. MMWR Recomm Rep. 2016; 65: 1-66

� 0.35 mg norethindrone daily

� Less effective than CHCs

� More irregular and unpredictable bleeding

� Therapy of choice for patients immediately postpartum, breastfeeding, or postabortion

Clinical Resource, Comparison of Oral Contraceptives and Non-Oral Alternatives. Pharmacist’s Letter/Prescriber’s Letter. February 2018.

Shrader SP, Ragucci KR., Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.

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� Must be taken at approximately the same time everyday to maintain contraceptive efficacy

� Missed dose = > 3 hours past intended administration

Curtis KM, et al. MMWR Recomm Rep. 2016; 65: 1-66

� Intramuscular or subcutaneous dosage forms

� Dose is repeated every 3 months (13 weeks)

› Can extend up to 15 weeks without backup

contraception use

� Can expect spotting and irregular periods for ~6 months. Most women develop amenorrhea

� Has increased incidence of weight gain (~3.7 kg over 2 years)

Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2019; Feb 22, 2019.

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� Subdermal implant

� Intrauterine devices (IUDs)

� Incidence of use is increasing

› From 2002 to 2012, IUD use in the U.S.

increased from 2% to 10% of all

contraception

� Little or nothing to remember to maintain efficacy

Madden T. Intrauterine contraception: Background and device types. In: UpToDate, Schreiber CA (Ed), UpToDate, Eckler K. (Accessed on March 1, 2019.)

� Nexplanon® (etonogestrel) 68 mg

� Releases ~65 mcg daily x 1 month, ~40 mcg daily x 1 year, ~35 mcg daily x 1 year, and then ~30 mcg daily x 1 year

� Can be left inserted for 3 years

� Most common adverse effect is irregular bleeding. Some women may develop amenorrhea


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� Mean levonorgestrel released is ~6 to ~15 mcg/day.

� Products provide either 3 or 5-year treatment lengths

� Require a follow-up 4-6 weeks after insertion to confirm placement

� Can expect increased bleeding or spotting for 3-6 months after placement. Some women develop amenorrhea.


Curtis KM, et al. MMWR Recomm Rep. 2016; 65: 1-66.

� Non-hormonal

� 10-year treatment length

� Works by inhibiting sperm transport and egg fertilization

� Most common adverse effect is heavier, longer periods with spotting in between for 2-3 months (heavier bleeding than hormonal contraceptives)

� Contraindicated in Wilson’s Disease

Package insert. Paragard (intrauterine copper contraceptive). Trumball, CT: Copper Surgical, 2018.

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Regimen Formulation

Timing of Use After

Unprotected Sexual

Intercourse

Mechanism of Action

FDA Labeled for EC Use

Selective progesterone

receptor modulator

1 tablet of 30 mg ulipristal

acetateUp to 5 days

Inhibit or delay ovulation,

inhibits follicular rupture

Yes

Progestin only

1 tablet of 1.5 mg

levonorgestrel

2 tablets of 0.75 levonorgestrel

Up to 3 daysInhibit or delay

ovulation, delays follicular development

Yes

Progestin and estrogen pills

A variety can be used

Up to 5 days No

Copper IUD N/A Up to 5 daysAffects sperm motility and

functionNo

HCP, health-care professional; OTC, over-the-counterACOG., ACOG Practice Bulletin. 2015; 152: 1-11.

� Adverse Effects› Nausea

› Headache

› Irregular Bleeding

› Abdominal Cramping

� Any EC may be used by women with contraindications to traditional oral contraceptives

� Can begin using hormonal contraceptives 5 days after ulipristal use and immediately after levonorgestrel ± estrogen EC use

ACOG., ACOG Practice Bulletin. 2015; 152: 1-11.

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Contraceptive Adverse Effect

CHCs Venous thromboembolism (VTE)

CHCsStroke (in the setting of migraines with

aura)

Depot Medroxyprogesterone

Loss of bone mineral density

LNG - IUD Pelvic inflammatory disease

Other serious risks exist, mostly when used for indications other than contraception

� No contraindication based on age alone

� Age is an independent risk factor for cardiovascular disease (CVD) and thromboembolism

� Avoid estrogen-containing contraceptives

� If the patient smokes, estrogen is contraindicated

ACOG., ACOG Practice Bulletin. 2019; 133: e128-e150.

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� Share common risk factors with VTE

� Estrogen may increase the risk of hypercoagulability and stroke

� Estrogen may increase blood pressure

� Estrogen may increase triglycerides; progestins may increase LDL

� As the number of risk factors increases, the amount of consideration for hormonal contraceptive use should decrease


� Hormonal contraception can worsen or cause recurrence of disease

� All hormonal methods of contraception are considered an unacceptable health risk in patients with current cancer

� In those who have no evidence of disease for 5 years, the risks of hormonal contraception usually outweigh the benefits

� The Cu-IUD is the preferred methodACOG., ACOG Practice Bulletin. 2019; 133: e128-e150.


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� Anticonvulsant medications induce hepatic clearance of estrogen and progestin and decrease serum concentrations

› Carbamazepine, oxcarbazepine,

phenobarbital, phenytoin, primidone

� Depot injections and IUDs are preferred treatment for this reason

� If using CHCs consider drug dosages, half-lives, and interruptions when choosing a product


� Studies have shown obese women require twice as long to reach steady state with pill formulations

� Continuous-cycle or higher-dose estrogen products may be more effective

� Due to potential for reduced efficacy, the transdermal patch is not recommended in women >90 kg

� LNG-IUD and Cu-IUD efficacy not affected by body weight


Clinical Resource, Contraception for Women with Chronic Medical Conditions. Pharmacist’s Letter/Prescriber’s Letter. September 2016.

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� Efficacy may be impaired in women who have undergone surgery that may impair oral absorption (Roux-en-Y bypass)

� Preference non-oral formulations in these patients

� All forms of contraception are acceptable in women who have had restrictive-type procedures (banding, sleeves)


� Do not use CHCs for 3 weeks after delivery due to increased risk for VTE

› If additional VTE risk factors, avoid for 6

weeks after delivery

� Can receive progestin-only methods immediately

� CHCs can be started immediately after a first or second trimester abortion


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� LNG-IUD may be used immediately postpartum or following first or second trimester abortion.*

� Cu-IUD can either be placed immediately postpartum or in the second postpartum month*

*assuming normal uterus position after delivery


Package insert. Paragard (intrauterine copper contraceptive). Trumball, CT: Copper Surgical, 2018.

� Do not use CHCs for 4 weeks after delivery due to increased VTE risk and decreased breastmilk production

� If additional VTE risk factors, avoid for 6 weeks after delivery

� Can receive progestin-only methods immediately

� Lactation has been associated with an increased risk of IUD perforation



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� Has been difficult to accomplish while maintaining libido

� Nestorone®/Testosterone transdermal gel

� Applied once daily to the shoulders and upper arms

� A phase II study is currently in progress

Popcouncil. 2018. https://www.popcouncil.org/news/20662.

� U.S. Selected Practice Recommendations for Contraceptive Use, 2016

› https://www.cdc.gov/mmwr/volumes/65/rr/

pdfs/rr6504.pdf

� The American College of Obstetricians and Gynecologists

› https://www.acog.org/Clinical-Guidance-

and-Publications/Search-Clinical-Guidance

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14-loflin-pharmacologic methods of contraception...hormonal contraception can worsen or cause...

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