• Clinical science

Hormonal contraceptives

Abstract

Hormonal contraceptives involve the use of estrogen and progestin analogs to prevent pregnancy. The contraceptive effect is mediated by negative feedback at the hypothalamus, ultimately leading to reduced pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Without an LH surge, ovulation does not occur. Progestin also makes implantation less likely, as it causes a thickening of cervical mucus, a decrease in tubal motility, and the inhibition of endometrial proliferation. Oral contraceptives (OCs) are the most common form of hormonal contraception, but other forms of hormone delivery, including patches, injections, and implants, also exist. In combination monophasic OCs, the dose of estrogen and progestin remains constant, while in combination multiphasic OCs it varies over the course of one cycle. The decreased total hormone doses of multiphasic OCs mitigate certain associated side effects and risks. These include bothersome symptoms such as breast tenderness, nausea, bloating, and breakthrough bleeding as well as medical emergencies such as venous thromboembolism. Because of the complications associated with hormonal contraceptives, their use is contraindicated in patients with certain medical conditions and histories, e.g., significant hypertension, ischemic heart disease, venous thromboembolism, and stroke.

Overview

Routine contraception

Description Pregnancy rate in first year with typical use (with perfect use) Indications
Oral contraceptive pill Combined oral contraceptive (COC)
  • Short-acting, reversible oral contraceptive containing estrogen and progestin
  • Monophasic or multiphasic
9% (< 1%)
Progestin-only contraceptive pills (minipill) 9% (< 1%)
  • Contraception for women in whom estrogen-containing contraceptives are contraindicated
Contraceptive patch
  • Short-acting, reversible contraceptive transdermal patch that provides sustained low doses of estrogen and progestin
9% (< 1%)
  • Patches are considered as effective as COC pills
  • Only require application to the skin once a week
  • Similar indications as for COC
Vaginal ring
  • Short-acting, reversible flexible vaginal ring that contains ethinyl estradiol and etonogestrel
9% (< 1%)
  • Similar indications as for COC
Injectable progestin
  • Intramuscular or subcutaneous injection administered every 3 months.
6% (< 1%)
  • Long-term and reversible
Intrauterine device with progestin
  • Need to be replaced every 3 to 5 years (varies with type of device).
< 1%
Subdermal Progestin implant
  • The device is usually inserted subdermally in the forearm and lasts 3 years.
< 1%

Emergency contraception

  • Non-hormonal methods: Copper-containing intrauterine devices
    • Added benefit of long-term contraception
    • Requires brief, clinical procedure
  • Hormonal methods
    • Most effective when taken within 3 days of intercourse
    • Typically administered as a single dose or as two doses over one day
    • Significantly less effective; in patients who are obese or overweight
    • Types
      • Levonorgestrel
      • Antiprogestin (e.g., ulipristal acetate)
      • Yuzpe regimen (combination of ethinyl estradiol and levonorgestrel)

The rate of pregnancy is ≤ 3.0% if emergency contraception is taken within 72 hours after unprotected sexual intercourse. The earlier it is taken, the lower the likelihood of pregnancy!

References:[1][2][3][4][5]

Effects

Mechanisms of action depend on the hormones used in the formulation

  • Estrogen
  • Progestin
    • Inhibits GnRH and LH secretion → suppresses ovulation
    • Inhibits endometrial proliferation
    • Changes cervical mucus (↓ volume and ↑ viscosity) and impairs fallopian tube peristalsis → inhibition of sperm ascension and egg implantation
    • Inhibits follicular maturation
  • Antiprogestin: inhibits or delays ovulation by inhibiting the progesterone receptor

Side effects

Common side effects

  • Estrogen:
    • Venous thromboembolism (VTE); (increased rate due to estrogen-mediated coagulopathy)
    • Cardiovascular events
    • Hypertension
      • Risk increased in patients with history of HTN during a pregnancy and/or family history of HTN
    • Headaches
    • Hepatic adenoma development
    • Mastopathy and mastodynia
    • Nausea
    • Enhanced fibroid growth with higher dose OCPs only (not in common use today)
  • Progestin:
  • Weight gain is not a side effect of hormonal contraceptives
Preparation Estrogen effect Androgen effect
Levonorgestrel antiestrogen androgen
Lynestrenol antiestrogen androgen
Norethisterone antiestrogen androgen
Desogestrel antiestrogen androgen
Dienogest almost no antiestrogen

antiandrogen

Indications for immediate discontinuation

Studies have shown that women taking estrogen-progestin combination OCPs before menopause have an increased risk of cervical carcinoma but a decreased risk of endometrial and ovarian carcinoma.

References:[6][7][8]

We list the most important adverse effects. The selection is not exhaustive.

Indications

Contraceptive indications

  • Patients desiring pregnancy in 1–2 years
    • Short-acting reversible options include OCPs, patches, and vaginal rings
    • DMPA is not appropriate for patients who wish to regain fertility soon
    • Implants and IUDs can be used but may not be cost-effective
  • Postpartum contraception: All contraceptive options except for combination OCPs can be considered in the postpartum period
    • OCPs containing estrogen should not be given if breastfeeding (estrogen may reduce breast milk production and enter the milk itself)
    • Combination OCPs may only be used after 4–6 weeks postpartum

Non-contraceptive indications

Contraindications

Absolute contraindications for estrogen-containing OCPs

Women who smoke and are > 35 years old should not be prescribed OCPs because of increased risk of cardiovascular side effects!

Relative contraindications for estrogen-containing OCPs

We list the most important contraindications. The selection is not exhaustive.

Special patient groups

Minors

In the United States, laws allowing minors to consent to contraceptive health care are determined by individual states. Most states allow adolescents to receive medical care related to pregnancy prevention without parental consent.