6 - Hormonal Contraception

What is the physiologic effect of estrogen in the follicular phase?

• secreted by mature follicle

• stimulates endometrium proliferation/differentiation

• induces progesterone receptors

• increases water content of cervical mucus

What is the physiologic effect of estrogen during ovulation?

level rises above threshhold for ~36hrs, triggering preovulatory surge of LH & FSH

What is the physiologic effect of estrogen in the luteal phase?

• corpus luteum produces small amounts

• stimulates muscle contractility in fallopian tubes

• declines in absence of fertilization

What is the physiologic effect of progesterone in the luteal phase?

prepares to maintain pregnancy

• stimulates secretory changes in endometrial lining

• thickens cervical mucus

• inhibits muscle contractility

What are the components of combined hormonal contraceptives?

• estrogen component = ethinyl estradiol

• progestin component = 17⍺-alkyl-19-nortestosterone derivative (estranes & gonanes)

Why can ethinyl estradiol be given orally?

ethinyl group at C17, increases oral potency & inhibits hepatic 1st pass

What is the main MOA of combination contraceptives?

prevent ovulation

What is the role of progestin in preventing ovulation in combined contraceptives?

• ↓ GnRH pulse frequency

• ↓ LH pulse frequency

• ↓ mid-cycle LH surge

What is the role of estrogen in preventing ovulation in combined contraceptives?

• ↓ FSH during follicular phase → no follicular development

• ↓ endogenous estrogen & progestin

What is notable about combination contraceptives?

combination is more effective to prevent ovulation than either alone

What is the minor action of combination contraceptives?

progestin:

• ↓ sperm transit (thickened cervical mucus)

• ↓ implantation

What are the 2 types of oral contraceptive preparations?

1. monophasic = fixed doses of e/p in each active pil

2. bi- and triphasic = varying doses of e/p in active pills in an attempt to stimulate cyclic changes

What are the instructions for transdermal patch contraceptives?

• apply to buttock, abdomen, upper arm, torso

• 3 weeks on, 1 week off

What are the instructions for intravaginal ring contraceptives?

3 weeks on, 1 week off

What are the cardiovascular ADE of combination contraceptives?

• ↑ DVT & PE

  • greater risk in smokers >35yo, transdermal preparations

• ↑ BP

What are the cancer ADE of combination contraceptives?

increased risk of cervical cancer with long-term use in patients with chronic HPV infection

What are the general ADE of combination contraceptives?

• breakthrough bleeding

• nausea

• edema

• headache

• ± acne

• ± hirsutism

What are the contraindications of combination contraceptives?

• thromboembolic disease

• cerebrovascular disease

• MI

• coronary artery disease

• hyperlipidemia

• hormone-dependent cancers

• undiagnosed vaginal bleeding

• pregnancy

What is the main MOA of progestin only contraceptives?

↓ sperm transit & implantation by thickening cervical mucus & thinning endometrium lining

What is the secondary mechanism of progestin only contraceptives?

prevent ovulation

What is the efficacy of progestin only pills & IUDs?

only blocks ovulation in 60-80% of cycles

What is a progestin only oral contraceptive?

minipill *must be taken daily without interruption

What type of contraceptive is available OTC?

progestin only

What are the non-oral progestin only dosage forms available?

• injections

• subdermal implants

• IUDs

What product is a non-oral progestin only injection & what is it’s specific timing?

• depo-provera (medroxyprogesterone acetate)

• q 3months

• effects can last for 6-12 months past last injection

What product is a non-oral progestin only subdermal inplant & what is it’s specific timing?

• implanon

• implanted in the arm q 3-5yrs

What product is a non-oral progestin only IUD & what is it’s specific timing?

• levonorgestrel

• q 3-6yrs

• 20% of women are amenorrheic at 1yr after insertion

What are the ADE of progestin only contraceptives?

• irregular spotting, breakthrough bleeding

• acne

• hirsutism

• headache

• mood changes

• decreased bone mineral density

• weight gain

• site rxn

What are the rare ADE of IUDs?

• uterine perforation

• pelvic inflammatory disease

• ectopic pregnancy

What are the contraindications of progestin only contraceptives?

• undiagnosed vaginal bleeding

• benign or malignant liver disease

• breast cancer

What is the onset of action of combined & progestin only contraceptives?

• start on 1st day of period = immediate protection

• start any other time = use backup method for 7 days

What is the onset of action of copper IUDs?

immediate, can be used as emergency contraception

What is the return to fertility time period for combined contraceptives?

• if missed pill, take it ASAP and next pill at normal time

• if missed >2 pills, use backup for 7 days

What is the return to fertility time period for progestin only pills & IUDs?

immediate, use backup in >3 hours late or if IUD is expelled/removed

What should be the timeframe when switching between oral contraceptives?

immediate

What should be the timeframe when switching between oral, patch, ring, or IUD contraceptives?

overlap 7 days with new contraceptive method

What can impact the absorption of oral contraceptives?

• vomiting within 3 hours or persistent diarrhea >24hrs

• follow recommendations for a missed dose

How are hormonal contraceptives metabolized?

CYP450

• inducers decrease effectiveness

• inhibitors increase ADE

Which hormonal contraceptive products have no drug-drug interactions?

• depot-provera

• IUDs

What are the non-hormonal contraceptive options?

• copper IUD

• spermicides

• physical barriers

• surgical intervention

• vaginal gel

What is the MOA of copper IUDs?

• inflammation rxn in endometrium, impairs sperm viability, motility, and fertilization

• can be used as emergency contraception

What is the MOA of spermicides?

decreases sperm viability and motility

What are physical barrier methods?

condoms, sponges, diaphragms

What are contraceptive surgical interventions?

• tubal ligation

• vasectomy

What is the vaginal gel contraceptive and what is it’s MOA?

Phexxi

• contains lactic acid, citric acid, potassium bitartrate

• maintains vaginal pH, creases sperm mobility

What is the efficacy of Phexxi?

• effective for up to 1hr

• 93% effective to prevent pregnancy with perfect use

What are the ADE of Phexxi?

bladder/kidney infections

What are the non-contraceptive health benefits of hormonal contraceptives?

• statistically safer than pregnancy or childbirth

• more regular cycles (combination)

• decreased acne & hirsutism (combination)

What are the non-contraceptive health benefits of hormonal contraceptives regarding reproductive disease?

• ↓ risk of endometrial cancer by 50%, continues to protect for 15yrs after d/c

• ↓ incidence of ovarian cysts and benign fibrocystic breast disease

• ↓ pelvic inflamm. disease & ectopic pregnancy

• relieves endometriosis

What are the non-contraceptive health benefits of hormonal contraceptives regarding connective tissue?

• ↓ blood loss

• ↓ iron-deficiency anemia

• ↑bone mineral density (w/ estrogen)

What do hormonal contraceptives not protect against?

STIs

What agents are used for post-coital contraception?

• copper IUD

• levonorgestrel (plan B)

How soon must a copper IUD be implanted if used as post-coital contraception?

within 5-7 days

What is the MOA of levonorgestrel?

• synthetic progesterone

• inhibits ovulation & fertilization

How soon must levonorgestrel be used?

within 72hrs after intercourse

What agents are anti-progestins?

• ulipristal

• mifepristone (10-50mg)

What is the MOA of ulipristal?

• selective progesterone receptor modulator

• partial PR agonist, inhibiting ovulation

• inhibits LH release from hypothalamus & AP, inhibiting follicular rupture within ovary

• may also block implantation

What is the use of ulipristal?

emergency contraceptive, used within 5 days of intercourse

What are the ADE of ulipristal?

• headache

• abdominal pain

What is the MOA of mifepristone?

• progesterone receptor blocker

• blocks PRs in uterus

• blocks GCC receptors and androgen receptors

What is the clinical effect of mifepristone when blocking PRs in uterus?

• blastocyst detaches → ↓ progesterone → decidual breakdown

• ↑ prostaglandin levels → uterine contractions

• softens cervix

What are the ADE of mifepristone?

• adrenal insufficiency

• increased ACTH and cortisol

How soon must mifepristone be used as emergency contraceptive?

within 5 days

What agents are abortifacients?

• mifepristone (600mg)

• misoprostol (400 μg)

How soon must mifeprisone be used as an abortifacient?

within 49 days after the start of the last period

What is the MOA of misoprostol?

• synthetic PGE1 analogue

• stimulates uterine contractions

• cervix dilation

What abortifacient agent is sometimes used before IUD insertion?

misoprostol

What are the ADE of abortifacients?

• severe vaginal bleeding

• abdominal pain

• uterine cramps

• n/v, diarrhea

What is the BBW of mifepristone?

serious fatal infections & bleeding

What are the contraindications of abortifacients?

• chronic adrenal failure

• ectopic pregnancy

• hermorrhagic disorders

• anticoagulation therapy

• intrauterine device

• undiagnosed adrenal mass