Combined hormonal contraception

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.{{Cite web|title=Combined Hormonal Birth Control: Pill, Patch, and Ring|url=https://www.acog.org/en/womens-health/faqs/combined-hormonal-birth-control-pill-patch-ring|access-date=2021-09-13|website=www.acog.org|language=en}} 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.{{Cite journal|last1=Wright|first1=Kristen Page|last2=Johnson|first2=Julia V|date=2008|title=Evaluation of extended and continuous use oral contraceptives|journal=Therapeutics and Clinical Risk Management|volume=4|issue=5|pages=905–911|doi=10.2147/tcrm.s2143|issn=1176-6336|pmc=2621397|pmid=19209272 |doi-access=free }}

Combined oral contraceptives (COCs) can be used to treat menstrual cycle disorders including heavy menstrual bleeding,{{Cite journal|last1=Matteson|first1=Kristen A.|last2=Rahn|first2=David D.|last3=Wheeler|first3=Thomas L.|last4=Casiano|first4=Elizabeth|last5=Siddiqui|first5=Nazema Y.|last6=Harvie|first6=Heidi S.|last7=Mamik|first7=Mamta M.|last8=Balk|first8=Ethan M.|last9=Sung|first9=Vivian W.|date=March 2013|title=Nonsurgical management of heavy menstrual bleeding: a systematic review|journal=Obstetrics and Gynecology|volume=121|issue=3|pages=632–643|doi=10.1097/AOG.0b013e3182839e0e|issn=1873-233X|pmc=4414119|pmid=23635628}} and pelvic pain disorders such as endometriosis{{Cite journal|last1=Zorbas|first1=Konstantinos A.|last2=Economopoulos|first2=Konstantinos P.|last3=Vlahos|first3=Nikos F.|date=July 2015|title=Continuous versus cyclic oral contraceptives for the treatment of endometriosis: a systematic review|url=https://pubmed.ncbi.nlm.nih.gov/25644508/|journal=Archives of Gynecology and Obstetrics|volume=292|issue=1|pages=37–43|doi=10.1007/s00404-015-3641-1|issn=1432-0711|pmid=25644508|s2cid=23340983}} and dysmenorrhea.{{Cite journal|last1=Wong|first1=Chooi L.|last2=Farquhar|first2=Cindy|last3=Roberts|first3=Helen|last4=Proctor|first4=Michelle|date=2009-10-07|title=Oral contraceptive pill for primary dysmenorrhoea|journal=The Cochrane Database of Systematic Reviews|volume=2009 |issue=4|pages=CD002120|doi=10.1002/14651858.CD002120.pub3|issn=1469-493X|pmc=7154221|pmid=19821293}} CHCs are also a first line treatment for polycystic ovary syndrome for menstrual abnormalities, acne, and hirsutism.{{Cite journal|last1=Legro|first1=Richard S.|last2=Arslanian|first2=Silva A.|last3=Ehrmann|first3=David A.|last4=Hoeger|first4=Kathleen M.|last5=Murad|first5=M. Hassan|last6=Pasquali|first6=Renato|last7=Welt|first7=Corrine K.|date=December 2013|title=Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline|journal=The Journal of Clinical Endocrinology and Metabolism|volume=98|issue=12|pages=4565–4592|doi=10.1210/jc.2013-2350|issn=1945-7197|pmc=5399492|pmid=24151290}}

Perimenopausal women on combined oral contraceptives have increased bone density,{{Cite journal|date=2006-05-20|title=Longitudinal evaluation of perimenopausal bone loss: Effects of different low dose oral contraceptive preparations on bone mineral density|url=https://www.sciencedirect.com/science/article/abs/pii/S0378512205002847|journal=Maturitas|language=en|volume=54|issue=2|pages=176–180|doi=10.1016/j.maturitas.2005.10.007|issn=0378-5122|last1=Gambacciani|first1=Marco|last2=Cappagli|first2=Barbara|last3=Lazzarini|first3=Veronica|last4=Ciaponi|first4=Massimo|last5=Fruzzetti|first5=Franca|last6=Genazzani|first6=Andrea Riccardo|pmid=16332417|url-access=subscription}} and COCs can be used to decrease hot flashes.{{Cite journal|last1=Allen|first1=Rebecca H.|last2=Cwiak|first2=Carrie A.|last3=Kaunitz|first3=Andrew M.|date=2013-04-16|title=Contraception in women over 40 years of age|url=https://www.cmaj.ca/content/185/7/565|journal=CMAJ|language=en|volume=185|issue=7|pages=565–573|doi=10.1503/cmaj.121280|issn=0820-3946|pmid=23460635|pmc=3626808}} Combined oral contraceptives have been shown to reduce risk of endometrial cancer, BRCA1 and BRCA2 ovarian cancer, and a modest reduction in colon cancer.{{Cite journal|last1=Iversen|first1=Lisa|last2=Sivasubramaniam|first2=Selvaraj|last3=Lee|first3=Amanda J.|last4=Fielding|first4=Shona|last5=Hannaford|first5=Philip C.|date=June 2017|title=Lifetime cancer risk and combined oral contraceptives : the Royal College of General Practitioners' Oral Contraception Study|url=https://pubmed.ncbi.nlm.nih.gov/28188769/|journal=American Journal of Obstetrics and Gynecology|volume=216|issue=6|pages=580.e1–580.e9|doi=10.1016/j.ajog.2017.02.002|issn=1097-6868|pmid=28188769|hdl=2164/10010|s2cid=205372611|hdl-access=free}}

• Combined injectable contraceptive,Hassan EO and El-Gibaly OM Combination injectable contraceptives for contraception : RHL commentary (last revised: 1 October 2009). The WHO Reproductive Health Library; Geneva: World Health Organization. additional category of CHC not available in the USA or UK{{Cite book|last=Guillebaud|first=John|url=https://www.worldcat.org/oclc/1002851042|title=Contraception : your questions answered|date=2017|others=Anne MacGregor|isbn=978-0-7020-7000-6|edition=Seventh|location=[Amsterdam]|oclc=1002851042}}
• The Faculty of Sexual and Reproductive Healthcare has issued guidelines for incorrect use
• 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.{{Cite web|title=FSRH Clinical Guideline: Combined Hormonal Contraception (January 2019, Amended November 2020) - Faculty of Sexual and Reproductive Healthcare|url=https://www.fsrh.org/standards-and-guidance/documents/combined-hormonal-contraception/|access-date=2021-09-13|website=www.fsrh.org}}

File:Hypothalamic–pituitary–gonadal axis in females.png

Prevention of ovulation occurs via inhibition of the hypothalamic–pituitary–gonadal axis, 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.{{Cite journal|last1=Rivera|first1=Roberto|last2=Yacobson|first2=Irene|last3=Grimes|first3=David|date=November 1999|title=The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices|url=https://doi.org/10.1016/S0002-9378(99)70120-1|journal=American Journal of Obstetrics and Gynecology|volume=181|issue=5|pages=1263–1269|doi=10.1016/s0002-9378(99)70120-1|pmid=10561657|issn=0002-9378|url-access=subscription}} Progesterone also contributes to the contraceptive effect by making changes to the cervical mucus, endometrium and tubal motility.

Although the risk of venous thromboembolism, arterial thromboembolism, breast cancer and cervical cancer 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.{{Cite web|title=Hormonal Contraception and Risk of Breast Cancer|url=https://www.acog.org/en/Clinical/Clinical%20Guidance/Practice%20Advisory/Articles/2018/01/Hormonal%20Contraception%20and%20Risk%20of%20Breast%20Cancer|access-date=2020-08-10|website=www.acog.org|language=en}}{{Cite web|date=2018-03-01|title=Oral Contraceptives (Birth Control Pills) and Cancer Risk - National Cancer Institute|url=https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet|access-date=2020-08-10|website=www.cancer.gov|language=en}} 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.{{Cite web|title=FSRH Clinical Guideline: Combined Hormonal Contraception (January 2019, Amended February 2019) – Faculty of Sexual and Reproductive Healthcare|url=https://www.fsrh.org/standards-and-guidance/documents/combined-hormonal-contraception/|access-date=22 July 2019|website=www.fsrh.org}}WHO | Medical eligibility criteria for contraceptive use (2015) p.121-132 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.{{Cite journal|title=Contraceptive pills and venous thrombosis|url=https://www.cochrane.org/CD010813/FERTILREG_contraceptive-pills-and-venous-thrombosis|access-date=2020-08-10|journal=The Cochrane Database of Systematic Reviews|year=2014|doi=10.1002/14651858.CD010813.pub2|pmid=24590565|language=en|last1=De Bastos|first1=M.|last2=Stegeman|first2=B. H.|last3=Rosendaal|first3=F. R.|last4=Van Hylckama Vlieg|first4=A.|last5=Helmerhorst|first5=F. M.|last6=Stijnen|first6=T.|last7=Dekkers|first7=O. M.|issue=3|pages=CD010813|pmc=10637279}}

Other adverse effects include nausea, headaches, breast pain, skin pigmentation, irregular menstrual bleeding, absent periods and irritation from contact lenses. Changes in libido and mood, decline of liver function and raised blood pressure may also occur.

{{Risk of venous thromboembolism with hormone therapy and birth control pills (QResearch/CPRD)}}

The estrogen in combined hormonal contraception can increase the risk of blood 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.{{Cite web|title=Hormonal Birth Control: Risk of Blood Clots {{!}} Michigan Medicine|url=https://www.uofmhealth.org/health-library/tw9278|access-date=2021-09-20|website=www.uofmhealth.org}}{{Cite web|date=2019-10-06|title=CDC - Combined Hormonal Contraceptives - US SPR - Reproductive Health|url=https://www.cdc.gov/reproductivehealth/contraception/mmwr/spr/combined.html|access-date=2021-09-20|website=www.cdc.gov|language=en-us}} 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.{{Cite web|title=Hormonal Contraception and Risk of Breast Cancer|url=https://www.acog.org/en/clinical/clinical-guidance/practice-advisory/articles/2018/01/hormonal-contraception-and-risk-of-breast-cancer|access-date=2021-09-20|website=www.acog.org|language=en}} 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.{{Cite journal|last=Moodley|first=Jack|date=February 2004|title=Combined oral contraceptives and cervical cancer|url=https://pubmed.ncbi.nlm.nih.gov/15128004/|journal=Current Opinion in Obstetrics & Gynecology|volume=16|issue=1|pages=27–29|doi=10.1097/00001703-200402000-00006|issn=1040-872X|pmid=15128004|s2cid=20566872}} Combined hormonal contraceptives are also associated with a decreased risk of endometrial, ovarian, and colorectal cancers.{{Cite web|date=2018-03-01|title=Oral Contraceptives (Birth Control Pills) and Cancer Risk - National Cancer Institute|url=https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet|access-date=2021-09-20|website=www.cancer.gov|language=en}}

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.{{Cite web|title=Combined Hormonal Birth Control: Pill, Patch, and Ring|url=https://www.acog.org/en/womens-health/faqs/combined-hormonal-birth-control-pill-patch-ring|access-date=2021-09-20|website=www.acog.org|language=en}} 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.{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK441582/|title=Contraception: Do hormonal contraceptives cause weight gain?|date=2017-06-29|publisher=Institute for Quality and Efficiency in Health Care (IQWiG)|language=en}}

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.{{Cite journal|last1=Lewis|first1=Carolin A.|last2=Kimmig|first2=Ann-Christin S.|last3=Zsido|first3=Rachel G.|last4=Jank|first4=Alexander|last5=Derntl|first5=Birgit|last6=Sacher|first6=Julia|date=2019|title=Effects of Hormonal Contraceptives on Mood: A Focus on Emotion Recognition and Reactivity, Reward Processing, and Stress Response|journal=Current Psychiatry Reports|volume=21|issue=11|page=115|doi=10.1007/s11920-019-1095-z|issn=1523-3812|pmc=6838021|pmid=31701260}}

{{Further information|Progestogen (medication)#Mood changes}}

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.

Should a woman have taken ulipristal acetate (ellaOne) for emergency contraception, restarting CHC may reduce ellaOne's effectiveness, hence advice is to wait five days before commencing CHC.

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.

Medications used in the treatment of epilepsy can interact with the combined pill, patch or vaginal ring,{{Cite web|url=https://www.epilepsy.org.uk/info/contraception/lamotrigine|title=Lamotrigine and contraception {{!}} Epilepsy Action|website=www.epilepsy.org.uk|language=en|access-date=14 August 2019|archive-date=14 August 2019|archive-url=https://web.archive.org/web/20190814104629/https://www.epilepsy.org.uk/info/contraception/lamotrigine|url-status=dead}} resulting in both pregnancy and shift in seizure threshold.{{Cite journal|last1=Reimers|first1=Arne|last2=Brodtkorb|first2=Eylert|last3=Sabers|first3=Anne|date=1 May 2015|title=Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations|journal=Seizure|series=Gender Issues in Epilepsy|volume=28|pages=66–70|doi=10.1016/j.seizure.2015.03.006|pmid=25843765|issn=1059-1311|doi-access=free}}

Based on a study of 16 women using oral CHC 30 μg ethinyloestradiol/150 μg levonorgestrel and anti-epileptic drug lamotrigine 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 instead may be preferable.

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.WHO Medical eligibility criteria for contraceptive use (2015) p. 7

When considering CHC use by age only, use is unrestricted between menarche and age 40, and can be generally used after age 40.

If someone is less than 21 days postpartum, they should not use combined hormonal contraceptives, according to the Centers for Disease Control and Prevention. If someone is postpartum and they also have risk factors for venous thrombosis, they should wait 21-42 days before using CHC. Within 42 days postpartum, all patients can use CHC.{{Cite web |last=CDC |date=2024-11-19 |title=Combined Hormonal Contraceptives |url=https://www.cdc.gov/contraception/hcp/usspr/combined-hormonal-contraceptives.html |access-date=2025-03-25 |website=Contraception |language=en-us}}

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.WHO Medical eligibility criteria for contraceptive use (2015) p. 28

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.{{Cite web|date=2019-06-07|title=Products - Data Briefs - Number 327 - December 2018|url=https://www.cdc.gov/nchs/products/databriefs/db327.htm|access-date=2021-09-13|website=www.cdc.gov|language=en-us}} 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.{{Cite journal|last=Brynhildsen|first=Jan|date=October 2014|title=Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks|journal=Therapeutic Advances in Drug Safety|volume=5|issue=5|pages=201–213|doi=10.1177/2042098614548857|issn=2042-0986|pmc=4212440|pmid=25360241}} 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.

CHC has been used worldwide for more than 60 years, with the first clinical trials on oral CHC beginning in 1956.{{Cite web|url=https://www.fpa.org.uk/factsheets/contraception-past-present-future|title=Contraception: past, present and future factsheet|date=15 June 2013|website=FPA|language=en|access-date=24 July 2019}}

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.{{Cite journal|last=Kao|first=Audiey|date=2000-06-01|title=History of Oral Contraception|url=https://journalofethics.ama-assn.org/article/history-oral-contraception/2000-06|journal=AMA Journal of Ethics|volume=2|issue=6|pages=55–56|doi=10.1001/virtualmentor.2000.2.6.dykn1-0006|pmid=23270650|issn=2376-6980|url-access=subscription}}

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.{{Cite web|title=Contraceptive Vaginal Rings {{!}} GLOWM|url=http://www.glowm.com/section-view/heading/contraceptive-vaginal-rings/item/395|access-date=2021-09-20|website=www.glowm.com|language=en}}

The first birth control patch, "Ortho Evra" was first introduced in 2002.{{Cite web|title=Ortho Evra — A New Transdermal Birth Control Patch {{!}} 2002-01-01 {{!}} AHC Media: Continuing Medical Education Publishing|url=https://www.reliasmedia.com/articles/118645-ortho-evra-8212-a-new-transdermal-birth-control-patch|access-date=2021-09-20|website=www.reliasmedia.com}} In 2014, a generic version of Ortho Evra was released and called "Xulane".{{Cite web|title=Xulane (ethinyl estradiol and norelgestromin) FDA Approval History|url=https://www.drugs.com/history/xulane.html|access-date=2021-09-20|website=Drugs.com|language=en}} In 2020, the FDA approved Twirla, a low-dose transdermal combined hormonal contraceptive.{{Cite web|title=FDA Approves Twirla (levonorgestrel and ethinyl estradiol) Contraceptive Patch|url=https://www.drugs.com/newdrugs/fda-approves-twirla-levonorgestrel-ethinyl-estradiol-contraceptive-patch-5161.html|access-date=2021-09-20|website=Drugs.com|language=en}}

• Progestogen-only contraception
• Combined oral contraceptive pill
• Contraceptive patch
• Contraceptive vaginal ring

{{Reflist}}

{{Hormonal contraception}}

{{Estrogens and antiestrogens}}

{{Progestogens and antiprogestogens}}

{{Estrogen receptor modulators}}

{{Progesterone receptor modulators}}

• [https://www.cochrane.org/CD003552/FERTILREG_skin-patch-or-vaginal-ring-compared-to-pills-for-birth-control Skin patch or vaginal ring compared to pills for birth control], Cochrane review (2013)

Category:Hormonal contraception

Category:Family planning