Combined hormonal contraception

Last updated
Combined hormonal contraception
Background
TypeHormonal
First use
  • oral pill - 1960
  • injection – 1960s
  • patch – 2003
  • vaginal ring – 2009
Failure rates (first year)
Perfect use0.3 [1] %
Typical use9 [1] %
Usage
Reversibilityon discontinuation
User reminders?
Advantages and disadvantages
STI protectionNo
PeriodsTypically regular and lighter
WeightNo evidence of weight gain [1]

Combined hormonal contraception (CHC), or combined birth control, is a form of hormonal contraception which combines both an estrogen and a progestogen in varying formulations. [1] [2]

Contents

The different types available include the pill, the patch and the vaginal ring, which are all widely available, [3] and an injection, which is available in only some countries. [4] They work by mainly suppressing luteinising hormone (LH) and follicle-stimulating hormone (FSH) and in turn preventing ovulation. [1]

The pill, patch, and vaginal ring are all about 93% effective with typical use. [5] Beneficial health effects include reduced risks of ovarian, endometrial and colorectal cancers. CHC can also provide improved control of some menstrual problems. Adverse effects include a small but higher risk of venous thromboembolism, arterial thromboembolism, breast cancer and cervical cancer. [4] [6]

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. [7] 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. [8]

Non-contraceptive use

Combined oral contraceptives (COCs) can be used to treat menstrual cycle disorders including heavy menstrual bleeding, [9] and pelvic pain disorders such as endometriosis [10] and dysmenorrhea. [11] CHCs are also a first line treatment for polycystic ovary syndrome for menstrual abnormalities, acne, and hirsutism. [12]

Perimenopausal women on combined oral contraceptives have increased bone density, [13] and COCs can be used to decrease hot flashes. [14] Combined oral contraceptives have been shown to reduce risk of endometrial cancer, BRCA1 and BRCA2 ovarian cancer, and a modest reduction in colon cancer. [14] [15]

Types

Types of Combined Hormonal ContraceptivesFormulationEfficacyPerfect Use
Combined oral contraceptive pill [7] Various formulations (10-50 μg estrogen (average 20–35) [16] and 0.05–3 mg progesterone [17] )9% failure rate with typical use (method not used consistently or correctly)

0.3% failure rate with perfect use

[7] [18]

Meant to be taken at the same time every day (some pills can be taken within 2–24 hours and still be effective) [19]
Combined contraceptive patch [7] 120-150 μg of norelgestromin and 20-35 μg ethinyl estradiol daily [20] [21] [22] New patch used once a week, after 3 weeks patch is not worn to allow for withdrawal bleeding [19]
Combined contraceptive vaginal ring [7] 120-150 μg etonogestrel and 13-15 μg ethinyl estradiol daily [20] [23] [24] Vaginal ring worn for 21 days and removed for the following 7 days to allow for withdrawal bleeding [19]
Hypothalamic-pituitary-adrenal axis Hypothalamic-pituitary-gonadal axis in females.png
Hypothalamic-pituitary-adrenal axis


Mechanism of action

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. [28] Progesterone also contributes to the contraceptive effect by making changes to the cervical mucus, endometrium and tubal motility. [28]

Treatment considerations

Adverse effects

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. [29] [30] 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. [31] [32] 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. [33]

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. [1]

Risk of venous thromboembolism (VTE) with hormone therapy and birth control (QResearch/CPRD)
TypeRouteMedications Odds ratio (95% CI Tooltip confidence interval)
Menopausal hormone therapy Oral Estradiol alone
    ≤1 mg/day
    >1 mg/day		1.27 (1.16–1.39)*
1.22 (1.09–1.37)*
1.35 (1.18–1.55)*
Conjugated estrogens alone
    ≤0.625 mg/day
    >0.625 mg/day		1.49 (1.39–1.60)*
1.40 (1.28–1.53)*
1.71 (1.51–1.93)*
Estradiol/medroxyprogesterone acetate 1.44 (1.09–1.89)*
Estradiol/dydrogesterone
    ≤1 mg/day E2
    >1 mg/day E2		1.18 (0.98–1.42)
1.12 (0.90–1.40)
1.34 (0.94–1.90)
Estradiol/norethisterone
    ≤1 mg/day E2
    >1 mg/day E2		1.68 (1.57–1.80)*
1.38 (1.23–1.56)*
1.84 (1.69–2.00)*
Estradiol/norgestrel or estradiol/drospirenone 1.42 (1.00–2.03)
Conjugated estrogens/medroxyprogesterone acetate 2.10 (1.92–2.31)*
Conjugated estrogens/norgestrel
    ≤0.625 mg/day CEEs
    >0.625 mg/day CEEs		1.73 (1.57–1.91)*
1.53 (1.36–1.72)*
2.38 (1.99–2.85)*
Tibolone alone1.02 (0.90–1.15)
Raloxifene alone1.49 (1.24–1.79)*
Transdermal Estradiol alone
   ≤50 μg/day
   >50 μg/day		0.96 (0.88–1.04)
0.94 (0.85–1.03)
1.05 (0.88–1.24)
Estradiol/progestogen 0.88 (0.73–1.01)
Vaginal Estradiol alone0.84 (0.73–0.97)
Conjugated estrogens alone1.04 (0.76–1.43)
Combined birth control Oral Ethinylestradiol/norethisterone 2.56 (2.15–3.06)*
Ethinylestradiol/levonorgestrel 2.38 (2.18–2.59)*
Ethinylestradiol/norgestimate 2.53 (2.17–2.96)*
Ethinylestradiol/desogestrel 4.28 (3.66–5.01)*
Ethinylestradiol/gestodene 3.64 (3.00–4.43)*
Ethinylestradiol/drospirenone 4.12 (3.43–4.96)*
Ethinylestradiol/cyproterone acetate 4.27 (3.57–5.11)*
Notes: (1) Nested case–control studies (2015, 2019) based on data from the QResearch and Clinical Practice Research Datalink (CPRD) databases. (2) Bioidentical progesterone was not included, but is known to be associated with no additional risk relative to estrogen alone. Footnotes: * = Statistically significant (p < 0.01). Sources: See template.

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. [34] [35] 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. [35]

Estrogens and progestins are metabolized in the liver, so there is a theoretical concern for use in women with liver disease. [35]

Large studies have shown a slight increased incidence of breast cancer among hormonal contraceptive users compared to nonusers. [36] However, the overall risk of breast cancer in users and nonusers remains low. [36] 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. [37] Combined hormonal contraceptives are also associated with a decreased risk of endometrial, ovarian, and colorectal cancers. [38]

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. [39] Breakthrough bleeding within the first 3–6 months is generally not harmful and often resolves with persistent use. [35]

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. [40]

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. [41]

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. [1]

Ulipristal acetate (ellaOne)

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. [1]

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. [1]

Antiepileptics

Medications used in the treatment of epilepsy can interact with the combined pill, patch or vaginal ring, [42] resulting in both pregnancy and shift in seizure threshold. [43]

Lamotrigine

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. [1]

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. [1] Long-acting reversible contraception instead may be preferable. [42]

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. [44]

Age

When considering CHC use by age only, use is unrestricted between menarche and age 40, and can be generally used after age 40. [2]

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. [45]

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. [46] 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. [47] 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. [1] 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. [47]

History

CHC has been used worldwide for more than 60 years, [1] with the first clinical trials on oral CHC beginning in 1956. [48]

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. [49]

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. [50]

The first birth control patch, "Ortho Evra" was first introduced in 2002. [51] In 2014, a generic version of Ortho Evra was released and called "Xulane". [52] In 2020, the FDA approved Twirla, a low-dose transdermal combined hormonal contraceptive. [53]

See also

Related Research Articles

<span class="mw-page-title-main">Combined oral contraceptive pill</span> Birth control method which is taken orally

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. It is the oral form of combined hormonal contraception. The pill contains two important hormones: a progestin and estrogen. When taken correctly, it alters the menstrual cycle to eliminate ovulation and prevent pregnancy.

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

<span class="mw-page-title-main">Contraceptive patch</span> Transdermal patch applied to prevent pregnancy

A contraceptive patch, also known as "the patch", is a transdermal patch applied to the skin that releases synthetic oestrogen and progestogen hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contraceptive pill with perfect use, and the patch may be more effective in typical use.

<span class="mw-page-title-main">Vaginal bleeding</span> Medical condition

Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproductive system, such as abnormal uterine bleeding.

Progestogen-only pills (POPs), colloquially known as "mini pills", are a type of oral contraceptive that contain synthetic progestogens (progestins) and do not contain estrogens. They are primarily used for the prevention of undesired pregnancy, although additional medical uses also exist.

<span class="mw-page-title-main">Ethinylestradiol</span> Estrogen medication

Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

Extended or continuous cycle combined oral contraceptive pills are a packaging of combined oral contraceptive pills (COCPs) that reduce or eliminate the withdrawal bleeding that would occur once every 28 days in traditionally packaged COCPs. It works by reducing the frequency of the pill-free or placebo days. Extended cycle use of COCPs may also be called menstrual suppression, although other hormonal medications or medication delivery systems may also be used to suppress menses. Any brand of combined oral contraceptive pills can be used in an extended or continuous manner by simply discarding the placebo pills; this is most commonly done with monophasic pills in which all of the pills in a package contain the same fixed dosing of a synthetic estrogen and a progestin in each active pill.

<span class="mw-page-title-main">Desogestrel</span> Medication

Desogestrel is a progestin medication which is used in birth control pills. It is also used in the treatment of menopausal symptoms in women. The medication is available and used alone or in combination with an estrogen. It is taken by mouth.

<span class="mw-page-title-main">Drospirenone</span> Medication drug

Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken by mouth.

<span class="mw-page-title-main">Estrogen patch</span> Transdermal delivery system for estrogens

An estrogen patch, or oestrogen patch, is a transdermal delivery system for estrogens such as estradiol and ethinylestradiol which can be used in menopausal hormone therapy, feminizing hormone therapy for transgender women, hormonal birth control, and other uses. Transdermal preparations of estrogen are metabolized differently than oral preparations. Transdermal estrogens avoid the first pass through the liver and thus potentially reduce the risk of blood clotting and stroke.

<span class="mw-page-title-main">Vaginal ring</span>

Vaginal 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 and provides contraception protection. Vaginal rings come in one size that fits most women.

Intermenstrual bleeding (IMB) is vaginal bleeding at irregular intervals between expected menstrual periods. It may be associated with bleeding with sexual intercourse.

<span class="mw-page-title-main">Contraceptive vaginal ring</span>

A contraceptive vaginal ring is a type of hormonal insert that is placed in the vagina for the purpose of birth control. The rings themselves utilize a plastic polymer matrix that is inlaid or embedded with contraceptive drug. This drug, often one or two hormones, is absorbed directly through the bloodstream through the cells that line the vaginal wall. Some vaginal rings contain both an estrogen and a progestin, which are available in Europe and the United States. Other vaginal rings contain just progesterone. The progesterone-only ring is only available in Latin America, exclusively for postpartum breastfeeding parents.

<span class="mw-page-title-main">Hormonal contraception</span> Birth control methods that act on the endocrine system

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 original hormonal method—the combined oral contraceptive pill—was first marketed as a contraceptive in 1960. In the ensuing decades, many other delivery methods have been developed, although the oral and injectable methods are by far the most popular. Hormonal contraception is highly effective: when taken on the prescribed schedule, users of steroid hormone methods experience pregnancy rates of less than 1% per year. Perfect-use pregnancy rates for most hormonal contraceptives are usually around the 0.3% rate or less. Currently available methods can only be used by women; the development of a male hormonal contraceptive is an active research area.

<span class="mw-page-title-main">Comparison of birth control methods</span>

There are many methods of birth control that vary in requirements, side effects, and effectiveness. As the technology, education, and awareness about contraception has evolved, new contraception methods have been theorized and put in application. Although no method of birth control is ideal for every user, some methods remain more effective, affordable or intrusive than others. Outlined here are the different types of barrier methods, hormonal methods, various methods including spermicides, emergency contraceptives, and surgical methods and a comparison between them.

Combined birth control pills that contain natural estradiol or an estradiol ester include:

<span class="mw-page-title-main">Estradiol (medication)</span> Steroidal hormone medication

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in feminizing hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

<span class="mw-page-title-main">Ethinylestradiol/etonogestrel</span> Pharmaceutical birth control combination

Ethinylestradiol/etonogestrel, sold under the brand names NuvaRing among others, is a hormonal vaginal ring used for birth control and to improve menstrual symptoms. It contains ethinylestradiol, an estrogen, and etonogestrel, a progestin. It is used by insertion into the vagina. Pregnancy occurs in about 0.3% of women with perfect use and 9% of women with typical use.

<span class="mw-page-title-main">Estrogen (medication)</span> Type of medication

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

Menstrual suppression refers to the practice of using hormonal management to stop or reduce menstrual bleeding. In contrast to surgical options for this purpose, such as hysterectomy or endometrial ablation, hormonal methods to manipulate menstruation are reversible.

References

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  28. 1 2 Rivera, Roberto; Yacobson, Irene; Grimes, David (November 1999). "The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices". American Journal of Obstetrics and Gynecology. 181 (5): 1263–1269. doi:10.1016/s0002-9378(99)70120-1. ISSN   0002-9378. PMID   10561657.
  29. ↑ "Hormonal Contraception and Risk of Breast Cancer". www.acog.org. Retrieved 2020-08-10.
  30. ↑ "Oral Contraceptives (Birth Control Pills) and Cancer Risk - National Cancer Institute". www.cancer.gov. 2018-03-01. Retrieved 2020-08-10.
  31. ↑ "FSRH Clinical Guideline: Combined Hormonal Contraception (January 2019, Amended February 2019) – Faculty of Sexual and Reproductive Healthcare". www.fsrh.org. Retrieved 22 July 2019.
  32. ↑ WHO | Medical eligibility criteria for contraceptive use (2015) p.121-132
  33. ↑ De Bastos, M.; Stegeman, B. H.; Rosendaal, F. R.; Van Hylckama Vlieg, A.; Helmerhorst, F. M.; Stijnen, T.; Dekkers, O. M. (2014). "Contraceptive pills and venous thrombosis". The Cochrane Database of Systematic Reviews (3): CD010813. doi:10.1002/14651858.CD010813.pub2. PMC   10637279 . PMID   24590565 . Retrieved 2020-08-10.
  34. ↑ "Hormonal Birth Control: Risk of Blood Clots | Michigan Medicine". www.uofmhealth.org. Retrieved 2021-09-20.
  35. 1 2 3 4 "CDC - Combined Hormonal Contraceptives - US SPR - Reproductive Health". www.cdc.gov. 2019-10-06. Retrieved 2021-09-20.
  36. 1 2 "Hormonal Contraception and Risk of Breast Cancer". www.acog.org. Retrieved 2021-09-20.
  37. ↑ Moodley, Jack (February 2004). "Combined oral contraceptives and cervical cancer". Current Opinion in Obstetrics & Gynecology. 16 (1): 27–29. doi:10.1097/00001703-200402000-00006. ISSN   1040-872X. PMID   15128004. S2CID   20566872.
  38. ↑ "Oral Contraceptives (Birth Control Pills) and Cancer Risk - National Cancer Institute". www.cancer.gov. 2018-03-01. Retrieved 2021-09-20.
  39. ↑ "Combined Hormonal Birth Control: Pill, Patch, and Ring". www.acog.org. Retrieved 2021-09-20.
  40. ↑ Contraception: Do hormonal contraceptives cause weight gain?. Institute for Quality and Efficiency in Health Care (IQWiG). 2017-06-29.
  41. ↑ Lewis, Carolin A.; Kimmig, Ann-Christin S.; Zsido, Rachel G.; Jank, Alexander; Derntl, Birgit; Sacher, Julia (2019). "Effects of Hormonal Contraceptives on Mood: A Focus on Emotion Recognition and Reactivity, Reward Processing, and Stress Response". Current Psychiatry Reports. 21 (11): 115. doi:10.1007/s11920-019-1095-z. ISSN   1523-3812. PMC   6838021 . PMID   31701260.
  42. 1 2 "Lamotrigine and contraception | Epilepsy Action". www.epilepsy.org.uk. Archived from the original on 14 August 2019. Retrieved 14 August 2019.
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  46. ↑ "Products - Data Briefs - Number 327 - December 2018". www.cdc.gov. 2019-06-07. Retrieved 2021-09-13.
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  49. ↑ Kao, Audiey (2000-06-01). "History of Oral Contraception". AMA Journal of Ethics. 2 (6): 55–56. doi:10.1001/virtualmentor.2000.2.6.dykn1-0006. ISSN   2376-6980. PMID   23270650.
  50. ↑ "Contraceptive Vaginal Rings | GLOWM". www.glowm.com. Retrieved 2021-09-20.
  51. ↑ "Ortho Evra — A New Transdermal Birth Control Patch | 2002-01-01 | AHC Media: Continuing Medical Education Publishing". www.reliasmedia.com. Retrieved 2021-09-20.
  52. ↑ "Xulane (ethinyl estradiol and norelgestromin) FDA Approval History". Drugs.com. Retrieved 2021-09-20.
  53. ↑ "FDA Approves Twirla (levonorgestrel and ethinyl estradiol) Contraceptive Patch". Drugs.com. Retrieved 2021-09-20.

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