Hormonal Birth Control Methods

• Combined hormonal birth control includes birth control pills, the birth control patch, and the vaginal birth control ring.
• Combined hormonal birth control releases estrogen and progestin into the whole body, preventing pregnancy mainly by stopping ovulation.
• It also causes other changes in the body that help to prevent pregnancy.
• Other hormonal birth control methods release only progestin.
• These include progestin-only pills, birth control injections ("shot"), and implants.
• Intrauterine devices ("IUDs") are long-acting reversible contraceptives.
• The IUDs can include the levonorgestrel IUD and the copper T IUD.

Contraceptive Use Statistics (2017-2019)

• 34.7% of women aged 15-49 in the United States were not currently using contraception.
• 65.3% of women aged 15-49 in the United States were currently using contraception.

Combined Hormonal Contraceptives

• Combined hormonal contraceptives release both a progestin and an estrogen.
• Types include combined oral contraceptives, transdermal contraceptive patches and vaginal contraceptive rings.

Mechanism of Action

• Combination hormonal contraceptives act by suppression of gonadotropins.
• The primary effect of gonadotropin suppression is the inhibition of ovulation.
• Other alterations include changes in the cervical mucus, which increase the difficulty of sperm entry into the uterus.
• Further alterations also affect the endometrium, which reduce the likelihood of implantation.

Progestin Actions

• Progestins have feedback actions at the hypothalamus and pituitary to inhibit LH and FSH secretion, preventing follicular development and ovulation.
• Progestins also promote the production of thick, sticky cervical mucus, which impairs sperm entry.
• Progestins can prevent pregnancy by promoting endometrial thinning.
• Progestins are synthetic forms of the natural hormone progesterone.

Estrogen Actions

• The estrogen component suppresses pituitary follicle-stimulating hormone (FSH) secretion.
• Low circulating FSH inhibits the formation of a dominant follicle in the ovary, reducing the likelihood of ovulation.
• Ethinyl estradiol is the estrogen in combined hormonal contraceptives and is a synthetic form of the natural hormone estradiol.

Combined Oral Contraceptives (COCs)

• COCs are the most commonly used form of hormonal contraception.
• Monophasic COCs: Every active pill contains the same amount of estrogen and progestin.
• Phasic COCs (mostly triphasic): Pills have low, medium, and high progestin amounts for weeks 1, 2, and 3.
• There are no differences in contraceptive efficacy among any of the FDA-approved COC formulations.
• Perfect use has a 0.2-0.3% failure rate.
• Typical use has a 4-7% failure rate.
• Ultra-low dose pills contain < 20 mcg ethinyl estradiol.
• Low dose pills contain 20-35 mcg ethinyl estradiol.
• High dose pills contain ≥ 50 mcg ethinyl estradiol.

Taytulla

• It consists of 28 soft gelatin capsules.
• 24 are pink and active, containing 1 mg norethindrone and 20 mcg ethinyl estradiol.
• 4 are maroon and non-hormonal placebos.
• Other monophasic COCs have different progestins, for example EE plus levonorgestrel, EE plus norgestimate, EE plus drospirenone

Xulane

• Delivers 0.15 mg/day of norelgestromin and 0.035 mg/day of ethinyl estradiol.

Benefits

• Therapeutic effects of Xulane are achieved at lower peak doses since first-pass hepatic metabolism and GI degradation of NGMN and EE do not occur.
• Plasma hormone levels remain relatively constant with Xulane.
• Sustained drug delivery reduces the need for frequent self-administration and may improve patient compliance.
• It is applied in a 4-week cycle with 3 weekly applications on the same day of the week, followed by a patch-free week

Warnings

• Higher estrogen exposure may increase the risk of adverse reactions, including venous thromboembolism (VTE).
• The Area Under the Curve (AUC) for ethinyl estradiol (EE) is approximately 60% higher in women using XULANE compared to oral contraceptives containing EE 35 mcg.

Vaginal Rings

• NuvaRing (and generic versions) and Annovera are flexible vaginal rings that continuously release a progestin (etonogestrel or segesterone, respectively) and an estrogen (ethinyl estradiol) into a woman's bloodstream.
• It is inserted in the vagina and must remain in place continuously for 3 weeks.
• Then it is followed by a 1-week ring-free interval.
• Annovera provides contraception for 13 cycles.

Benefits

• Protects against ovarian, endometrial, and colorectal cancers.
• Women who have ever used oral contraceptives have a 30% to 50% lower risk of ovarian cancer than women who have never used oral contraceptives.
• Endometrial cancer risk is decreased by at least 30%. Colorectal cancer risk is decreased by 15-20%.

Considerations

• Effectiveness may be reduced by concomitant use of drugs, especially if EE < 0.05 mg with strong CYP3A4 inducers like rifampin, phenobarbital, phenytoin, and carbamazepine.
• Effectiveness may be reduced by certain antibiotics besides rifampin.

Contradictions

• All Prescribing Information for combined hormonal contraceptives include a Warning and Precaution about breast cancer, as of April 2022.
• Combined hormonal contraceptives should not be used in females who currently have or have had breast cancer. Because breast cancer may be hormonally sensitive.
• Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk.

Deep Vein Thrombosis (DVT)

• DVT occurs when a blood clot (thrombus) forms in one or more of the deep veins in the body, usually in the legs.
• The clots can travel through the bloodstream and block blood flow in the lung (pulmonary embolism).
• Combined hormonal methods are associated with a small increased risk of DVT, heart attack, and stroke.
• The risk is higher in people older than 35 who smoke more than 15 cigarettes a day or who have multiple risk factors for cardiovascular disease, who have a history of stroke, heart attack, or DVT or who have a history of migraine headaches with aura.

When to avoid

• Combined Hormonal Contraceptives are in Category 4 (unacceptable health risk – not to be used) for women with current breast cancer, migraine with aura at any age, migraine without aura, age ≥ 35 years, smoking ≥ 15 cigarettes/day AND age ≥ 35, stage 2 hypertension (systolic ≥160 mm Hg or diastolic ≥100 mm Hg), acute DVT/PE or at higher risk for recurrent events, SLE positive (or unknown) for antiphospholipid antibodies

Progestin-only Hormonal Contraceptives

• The types include progestin-only pills, birth control injection ("Depo shot") and birth control implant.

Progestin-only Pills (POPs)

• Mini-pills use a daily progestin (a synthetic progesterone) to prevent pregnancy.
• Progestins thin the lining of the uterus to prevent embryo implantation.
• Progestins thicken cervical mucus to make it difficult for sperm to travel into the uterus to connect with an ovum (egg).
• POPs are prescribed to women who have migraines with aura, are breastfeeding, have high blood pressure, or have a history of blood clots or are at high risk of clots.
• There is a very tight window with POPs. If a dose is missed by 3 hours, a backup method like condoms must be employed. If the woman has had sex in the past 3 to 5 days, emergency contraception is recommended.

Depot Medroxyprogesterone Acetate

• It's injected IM every 3 months.
• Medroxyprogesterone acetate (MPA) inhibits the secretion of gonadotropins which primarily prevents follicular maturation and ovulation.
• MPA also causes thickening of cervical mucus.
• These actions produce its contraceptive effect.
• Common side effects include irregular menstrual bleeding, bone density loss, weight gain and delayed return of fertility.

Progestin Implant System – LARC

• Etonogestrel-releasing subdermal implant (Nexplanon) lasts for 3 years.
• The contraceptive effect is achieved by suppression of ovulation, increased viscosity of the cervical mucus, and alterations in the endometrium.
• There may be complications of insertion and removal.
• Reports of implant migration with neural and vascular injury have been related to deep insertion.
• Removal may be difficult or impossible if not inserted correctly.
• NEXPLANON consists of a single, radiopaque, rod-shaped implant, containing 68 mg etonogestrel, pre-loaded in the needle of a disposable applicator.

Emergency Contraception

• Four options are available in the US: Oral levonorgestrel (1.5 mg pill) in a single dose such as Plan B One-Step (OTC), Ulipristal acetate (UPA) in a single dose such as Ella (prescription required), high dose combined oral contraceptive pills (Yuzpe regimen) and placement of a copper IUD.

Levonorgestrel

• Levonorgestrel (1.5 mg within 72 hours) causes can either delay the process of follicular maturation or totally arrest the follicular development.

MOA

• This inhibits or delays ovulation, depending on the time of administration after selection of the dominant follicle.
• Exposure to levonorgestrel (LNG) during the pre-ovulatory phase can either delay the process of follicular maturation or totally arrest the follicular development.
• This inhibits or delays ovulation, depending on the time of administration after selection of the dominant follicle.
• Once the level of luteinizing hormone (LH) starts rising, LNG emergency contraceptive has no effect and cannot prevent ovulation.
• The primary mechanism of action of emergency oral contraception is the inhibition or delay of ovulation.

Ulipristal acetate (UPA)

• A progestin receptor agonist/antagonist that can prevent pregnancy after unprotected sex or contraceptive failure.
• It can be taken up to 120 hours (5 days) after unprotected sexual intercourse. The sooner it is taken, the more likely it will prevent pregnancy.

Medical Abortion

• A 20-yo college student who is 6 weeks pregnant goes to her local clinic for information on pregnancy termination. She is fearful of an operation and asks about medical abortion. Clinic staff explain that mifepristone can be used early in pregnancy for termination, with an efficacy rate of around 85%. When a second drug is administered 24-48 hours after taking mifepristone, efficacy rises to almost 100%. Prostaglandin E1 analog is administered shortly after mifepristone.

Mifepristone

• Functions as a PR antagonist.
• It is the first of two meds used in a medical abortion.
• It is taken orally.
• It must not be used if it has been more than 70 days (10wks) since the first day of the last menstrual period.
• Under the new FDA rules patients will still need a prescription from a certified health care provider, but any pharmacy that agrees to accept those prescriptions can dispense the pills in its stores and by mail order.

Misoprostol

• A PGE1 analog, is taken buccally (in the cheek pouch) 24-to-48 hours after mifepristone.
• Activates prostaglandin receptors in the uterine smooth muscle to promote uterine contraction and expulsion of contents.

IUDs - Intrauterine Devices

• Long-acting reversible contraceptives (LARCs)
• Intrauterine devices (IUDs) and contraceptive implants are long-acting reversible contraception (LARC).
• All IUDs are >99% effective as contraceptives.
• Paragard is a copper IUD while other IUDs are levonorgestrel (LNG) IUDs that release small amounts of levonorgestrel into the uterus each day.

IUD MOA

• The Copper T380A exerts its contraceptive effect primarily by preventing fertilization through inhibition of sperm migration and viability.
• LNG-IUDs have a similar primary mechanism of action by preventing fertilization by causing a profound change in the amount and viscosity of cervical mucus, making it impenetrable to sperm.

Pregnancy Rates

• Oral contraceptives exhibit one-year pregnancy rates of 79-95% with a median time to pregnancy of 2.5 to 3 cycles.
• Copper IUDs are at 71-91% for one-year pregnancy rates with a median time to pregnancy of 2 to 3.7 months.
• Levonorgestrel-releasing intrauterine systems display one-year pregnancy rates of 79-96% with a median time to pregnancy of 4 months.
• Implants show a one-year pregnancy rate of 76-86% with a median time to pregnancy being 2.9 to 4.4 months.
• Injectables exhibit at one-year pregnancy rate of 73-83% with the median time to pregnancy being 4.5 and 5 months.