- 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) |
| 9% (< 1%) |
|
Progestin-only contraceptive pills (minipill) |
| 9% (< 1%) |
| |
Contraceptive patch |
| 9% (< 1%) | ||
Vaginal ring |
| 9% (< 1%) |
| |
Injectable progestin |
| 6% (< 1%) |
| |
Intrauterine device with progestin |
| < 1% | ||
Subdermal Progestin implant |
| < 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
- Hypothalamus: ↓ release of GnRH
- Pituitary: ↓ LH → inhibits ovulation, ↓ FSH → prevents ovarian folliculogenesis
-
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
- Headaches
- Hepatic adenoma development
- Mastopathy and mastodynia
- Nausea
- Enhanced fibroid growth with higher dose OCPs only (not in common use today)
-
Progestin:
- Breakthrough bleeding
- Follicular cysts
- Venous thromboembolism (VTE)
- 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
- Sensory disorders (e.g., impaired vision)
- New or enhanced migraine-like headaches (especially with aura)
- New or enhanced epilepsy
- Detection of masses
- Jaundice
- Pregnancy
- Suspected thromboembolism or thrombophlebitis
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
Non-contraceptive indications
- Symptomatic treatment in menorrhagia and dysmenorrhea
- Polycystic ovary syndrome (PCOS)
- Menstrual migraine
- Premenstrual dysphoric disorder (PMDD)
-
Hyperandrogenism
- Acne
- Hirsutism
- Pelvic pain due to endometriosis
Contraindications
Absolute contraindications for estrogen-containing OCPs
-
Cardiovascular
- Thromboembolism
- Coagulopathy, antiphospholipid antibodies
- Coronary heart disease
- Stroke
- Arterial hypertension (> 160/95 mm Hg)
- Heart defects
-
Metabolic
- Pronounced hypertriglyceridemia
- Metabolic disorders of the liver
- Insulin-dependent diabetes mellitus
-
Oncologic
- Hepatic tumors
- Estrogen-dependent tumors
-
Inflammatory
- Acute pancreatitis
- Lupus erythematodes
- Vasculitis
- After herpes gestationis
- Smoking > 35 years of age
- Genital bleeding of unknown cause
- Pregnancy
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
-
Cardiovascular
- Superficial venous thrombosis
- Thrombophlebitis
- Severe varicosis
-
Metabolic
- Hypercholesterinemia
- Morbid obesity
- Diabetes mellitus
- Age > 40 years
- Epilepsy
- Migraines
- Smoking
- Lactation (progestin-only preparations permitted)
- Uterine leiomyomas (especially intracavitary)
- Gastric/duodenal ulcer
- Ulcerative colitis
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.