Contraception and Clinical Pharmacy

Introduction to Contraception

• Contraception is the prevention of pregnancy by inhibiting sperm from reaching a mature ovum or by preventing a fertilized ovum from implanting in the endometrium.
• Hormonal contraception is used by cis women and transgender individuals.

Menstrual Cycle Pathophysiology

• The median menstrual cycle length is 28 days, ranging from 21-40 days.
• The cycle consists of the follicular phase, ovulation, and the luteal phase.
• The hypothalamus secretes gonadotropin releasing hormone, which stimulates the anterior pituitary to secrete follicle stimulating hormone (FSH) and luteinizing hormone (LH).
• In the follicular phase, FSH levels increase, causing recruitment of a small group of follicles, and one of these becomes the dominant follicle.
• The dominant follicle develops increasing amounts of estradiol and inhibin, providing negative feedback on the secretion of gonadotropin releasing hormone and FSH.
• The dominant follicle continues to grow and synthesizes estradiol, progesterone, and androgen.
• Estradiol stops the menstrual flow from the previous cycle, thickens the endometrial lining, and produces thin, watery cervical mucus.
• The pituitary releases a midcycle LH surge that stimulates the final stages of follicular maturation and ovulation.
• Ovulation occurs 24-36 hours after the estradiol peak and 10-16 hours after the LH peak.
• The LH surge is the most clinically useful predictor of approaching ovulation.
• Conception is most successful when intercourse takes place from 2 days before ovulation to the day of ovulation.
• After ovulation, the remaining luteinized follicles become the corpus luteum, which synthesizes androgen, estrogen, and progesterone.
• If pregnancy occurs, human chorionic gonadotropin prevents regression of the corpus luteum and stimulates continued production of estrogen and progesterone.
• If pregnancy does not occur, the corpus luteum degenerates, progesterone declines, and menstruation occurs.

Treatment of Contraception

• The goal of treatment is the prevention of pregnancy from sexual intercourse.

Non-Pharmacologic Therapy

• The internal condom (female condom) covers the labia and cervix, with a higher pregnancy rate than external condoms, but protects against many viruses, including HIV.
• Do not use external and internal condoms together.
• Spermicides contain nonoxynol-9, a surfactant that destroys sperm cell walls and blocks entry into the cervical os.
• Spermicides offer no protection against STIs, and when used more than twice daily, nonoxynol-9 may increase HIV transmission.
• Phexxi is a prescription nonoxynol-9 free spermicide that reduces vaginal pH to reduce sperm motility, but carries a risk of cystitis.
• The vaginal contraceptive sponge is available over the counter and contains nonoxynol-9, providing protection for 24 hours.

Hormonal Contraceptives

• With perfect use, CHC efficacy is more than 99%, but with typical use, up to 7% of individuals will have unintended pregnancy.
• Monophasic CHCs contain a constant amount of estrogen and progestin for 21 days.
• Biphasic and triphasic pills contain variable amounts of estrogen and progestin for 21 days.
• Extended cycle pills and continuous combination regimens may reduce adverse effects and are more convenient.
• The progestin-only “minipills” are less effective than CHCs and are associated with irregular and unpredictable menstrual bleeding.
• The first day start method, Sunday start method, and quick start method are different ways to start hormonal contraception.

Transdermal Contraceptives

• Two combination contraceptives are available as a transdermal patch: Xulane and Twirla.
• Xulane delivers 35 mcgEE and 150 mcg norgestimate daily, while Twirla provides 120 mcg of levonorgestrel and 30 mcg of EE daily.
• These patches are effective as CHCs in individuals weighing less than 90 kg (198 lb) or having a BMI less than 30 kg/m2, with failure rates between 3% and 7%.
• Apply the patch to the abdomen, buttocks, upper torso, or upper arm at the beginning of the menstrual cycle and replace every week for 3 weeks.

Vaginal Rings

• There are two vaginal rings available: NuvaRing and Annovera.
• NuvaRing releases ∼15 mcg/day of EE and 120 mcg/day of etonogestrel, while Annovera releases 13 mcg of EE and 150 mcg of segesterone acetate.
• On first use, the ring should be inserted on or prior to the fifth day of the cycle, remain in place for 3 weeks, and then be removed.