Combined hormonal contraception (CHC), or combined birth control, is a form of

hormonal contraception Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origin ...

which combines both an

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

and a

progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

in varying formulations. The different types available include

the pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: proges ...

, the

patch Patch or Patches may refer to: Arts, entertainment and media * Patch Johnson, a fictional character from ''Days of Our Lives'' * Patch (''My Little Pony''), a toy * "Patches" (Dickey Lee song), 1962 * "Patches" (Chairmen of the Board song) ...

and the

vaginal ring Vaginal rings (also known as intravaginal rings, or V-Rings) are polymeric drug delivery devices designed to provide controlled release of drugs for intravaginal administration over extended periods of time. The ring is inserted into the vagina a ...

, which are all widely available, and an

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

, which is available in only some countries. They work by mainly suppressing

luteinising hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...

(LH) and

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...

(FSH) and in turn preventing

ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...

. The pill, patch, and vaginal ring are all about 93% effective with typical use. Beneficial health effects include reduced risks of

ovarian The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body ...

endometrial The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...

and

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

s. CHC can also provide improved control of some menstrual problems. Adverse effects include a small but higher risk of

venous thromboembolism Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to ...

arterial thromboembolism Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmona ...

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

and

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...

Medical use

Contraceptive use

With perfect use, less than 1% of women will become pregnant during the first year of using CHC. However, with typical use 9% of women will become pregnant during the first year. Traditionally, to mimic a normal menstrual cycle, CHC is used for 21 consecutive days. For all of these methods (pill, patch, vaginal ring), these 21 days are typically followed by either 7 days of no use (for the pill, patch or vaginal ring) or 7 days of administration of placebo pills (for the pill only). During these 7 days, withdrawal bleeding occurs. For those women who do not desire withdrawal bleeding or require bleeding to be suppressed completely, medication regimens can be tailored to the individual with extended periods of use and infrequent hormone-free periods. The efficacy of CHC is the same whether these methods are used continuously or with a 7-day break to allow for withdrawal bleeding.

Non-contraceptive use

Combined oral contraceptives (COCs) can be used to treat menstrual cycle disorders including heavy menstrual bleeding, and pelvic pain disorders such as

endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...

and

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...

. CHCs are also a first line treatment for

polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...

for menstrual abnormalities, acne, and hirsutism. Perimenopausal women on combined oral contraceptives have increased bone density, and COCs can be used to decrease hot flashes. Combined oral contraceptives have been shown to reduce risk of endometrial cancer, BRCA1 and BRCA2 ovarian cancer, and a modest reduction in colon cancer.

Types

Combined injectable contraceptive Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy. CICs are different from progestoge ...

, additional category of CHC not available in the USA or UK * The

Faculty of Sexual and Reproductive Healthcare The Faculty of Sexual and Reproductive Healthcare (FSRH) is a faculty of the Royal College of Obstetricians and Gynaecologists The Royal College of Obstetricians and Gynaecologists (RCOG) is a professional association based in London, Unite ...

has issued guidelines for incorrect use * Note: hormonal use for 21 days followed by 7 day withdrawal is the most common regimen however schedules are variable; Other factors affecting effectiveness include drug interactions, malabsorption and body weight Hypothalamic–pituitary–gonadal axis in females

Hypothalamic–pituitary–gonadal axis in females

Mechanism of action

Prevention of ovulation occurs via inhibition of the

hypothalamic–pituitary–adrenal axis The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland (a ...

, through progesterone and estrogen providing negative feedback to the hypothalamus and inhibiting the production of gonadotropin releasing hormone (GnRH). GnRH typically promotes the release of LH and FSH from the pituitary. The presence of estrogen in CHCs results in downstream inhibition of luteinizing hormone (LH) and follicular stimulating hormone (FSH) which typically act at the ovarian level to induce ovulation and promote development of the follicle respectively. Progesterone also contributes to the contraceptive effect by making changes to the cervical mucus,

endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...

and tubal motility.

Treatment considerations

Adverse effects

Although the risk of

and

in CHC users is small, all CHCs are associated with higher risks of these compared to no use. Given that the vast majority of the studies evaluating these associations have been observational studies, causation between CHC use and these conditions is unable to be determined. All CHCs are associated with an increased incidence of venous and arterial thromboembolism. However, those containing higher doses of estrogen are associated with an increase in venous and arterial thromboembolism. In addition, some formulations of progesterone, including gestodene, desogestrel, cyproterone acetate and drospirenone, in combination with estrogen, have been associated with higher rates of venous thromboembolism compared to formulations containing a type of progesterone called levonorgestrel. Other adverse effects include nausea, headaches, breast pain,

skin pigmentation Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from one's biological parents and or individu ...

, irregular menstrual bleeding, absent periods and irritation from contact lenses. Changes in

libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act up ...

and mood, decline of liver function and raised

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

may also occur.

Contraindications

The estrogen in combined hormonal contraception can increase the risk of clotting in some women. In particular, this can manifest as a deep vein thrombosis or pulmonary embolism. However, the risk with low-dose combined hormonal contraceptives remain relatively low in most cases. Health providers may recommend against formulations with estrogen in women with certain risk factors including personal or family history of blood clots, pregnancy and the first 3 weeks postpartum, obesity, inactivity, and coagulation disorders. Additionally, combined hormonal contraceptives are sometimes not recommended in the first 4–6 weeks postpartum after delivery due to concerns of effect on breastfeeding performance. Estrogens and progestins are metabolized in the liver, so there is a theoretical concern for use in women with liver disease. Large studies have shown a slight increased incidence of breast cancer among hormonal contraceptive users compared to nonusers. However, the overall risk of breast cancer in users and nonusers remains low. Research has also shown a link between cervical cancer and long-term use of combined hormonal contraception, particularly in women with chronic HPV infection of the cervix. Combined hormonal contraceptives are also associated with a decreased risk of endometrial, ovarian, and colorectal cancers.

Side effects

The most common side-effects of combined hormonal contraceptives include headache, nausea, breast tenderness, and breakthrough bleeding. Vaginal ring use can include additional side-effects including vaginal irritation and vaginal discharge. Contraceptive skin patch use can also include a side-effect of skin irritation around the patch site. Breakthrough bleeding within the first 3–6 months is generally not harmful and often resolves with persistent use. Contradictory research exists on the effects of combined hormonal contraceptives on weight gain. Clinical studies have shown some women report weight gain while others report weight loss. Several mechanisms for weight gain have been theorized including increased fluid retention, increase in muscle tissue, and increase in body fat. Many women stop taking combined hormonal contraceptives because they are concerned about weight gain; however, the link remains uncertain. The effect of combined hormonal contraceptives on mood is unclear at this point. There have been some large cohort studies suggesting there may be an association with mood-related side-effects. Patient-perceived changes in mood remain one of the most common reasons for hormonal contraceptive discontinuation.

Drug interactions

Liver enzyme inducing drugs

Medications that induce liver enzymes increase the metabolism of oestradiol and progestogens and subsequently may reduce the effectiveness of CHC. The advice on CHC also depends on whether the liver inducing drug is used short term, for less than two months, or long term, for more than two months.

Ulipristal acetate (ellaOne)

Should a woman have taken

ulipristal acetate Ulipristal acetate, sold under the brand name Ella among others, is a medication used for emergency contraception (birth control) and uterine fibroids. As emergency contraception it should be used within 120 hours of vaginally penetrating inter ...

(ellaOne) for

emergency contraception Emergency contraception (EC) is a birth control measure, used after sexual intercourse to prevent pregnancy. There are different forms of EC. Emergency contraceptive pills (ECPs), sometimes simply referred to as emergency contraceptives (ECs), o ...

, restarting CHC may reduce ellaOne's effectiveness, hence advice is to wait five days before commencing CHC.

Antibiotics

Extra contraceptive precautions are not necessary when using CHC in combination with antibiotics that do not induce liver enzymes, unless the antibiotics cause vomiting and/or diarrhoea.

Antiepileptics

Medications used in the treatment of epilepsy can interact with the combined pill, patch or vaginal ring, resulting in both pregnancy and shift in

seizure threshold The term seizure threshold is used to describe the balance between excitatory (glutaminergic) and inhibitory ( GABA-ergic) forces in the brain which affect how susceptible a person is to seizures. Those diagnosed with epilepsy or certain other neur ...

Lamotrigine

Based on a study of 16 women using oral CHC 30 μg ethinyloestradiol/150 μg levonorgestrel and anti-epileptic drug

lamotrigine Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut synd ...

for 6 weeks, it was revealed that the contraceptive effectiveness could be lowered, despite lamotrigine not being an enzyme inducer. An assessment of risks versus benefits of CHC is recommended in women on lamotrigine who are considering CHC, as the seizure threshold in someone on lamotrigine may be lowered by the oestrogen in CHC. In a similar mechanism, stopping CHC in a patient on lamotrigine can cause lamotrigine toxicity.

Long-acting reversible contraception Long-acting reversible contraceptives (LARC) are methods of birth control that provide effective contraception for an extended period without requiring user action. They include injections, intrauterine devices (IUDs), and subdermal contraceptiv ...

instead may be preferable.

Special populations

Following childbirth, the use of CHC depends on factors such as whether the mother is breastfeeding and whether she has other medical conditions including superficial venous thrombosis and dyslipidaemia.

Age

When considering CHC use by age only, use is unrestricted between

menarche Menarche ( ; ) is the first menstrual cycle, or first menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fertility. Gir ...

and age 40, and can be generally used after age 40.

Breastfeeding

CHC should not be used by breastfeeding women in the first six weeks after delivery and are generally not recommended in the first six months after delivery if still breastfeeding. After six months, breastfeeding women may use CHC.

Epidemiology

Between 2015 and 2017, 64.9% of women ages 15–49 in the United States were using contraception, and of those 12.6% were using the oral contraceptive pill. There are approximately 100 million users of combined oral contraceptives worldwide, with use being more common in Western Europe, Northern Europe, and the United States. In the UK, one survey demonstrated that in 2010–2012, more than 33% of women aged 16–44 years had used oral contraception in the previous year and that it was mostly the combined type. Between 2006 and 2010 only 10% of women in the US had used the contraceptive patch, and 6% had used the vaginal ring. Combined injectables are most common in China, South-East Asia and South America.

History

CHC has been used worldwide for more than 60 years, with the first clinical trials on oral CHC beginning in 1956. The FDA first approved the oral contraceptive in 1960. The first oral contraceptive contained 100 to 175 µg of estrogen and 10 mg of progesterone. However, at these levels significant adverse effects were seen and modern preparations contain lower levels of 30 to 50 µg of estrogen and 0.3 to 1 mg of progesterone. The first contraception vaginal ring was approved for use in the United States in 2001. Development of the ring has led to several designs with different sizes, ring materials, and steroid formulations. Modern designs are made of plastic polymer rings containing sex steroids which diffuse out of the ring directly into the vaginal epithelium and into systemic circulation. The first birth control patch, "Ortho Evra" was first introduced in 2002. In 2014, a generic version of Ortho Evra was released and called "Xulane". In 2020, the FDA approved Twirla, a low-dose transdermal combined hormonal contraceptive.

References

{{Progesterone receptor modulators