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Hormonal contraception refers to
birth control
Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
methods that act on the
endocrine system
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
. Almost all methods are composed of
steroid hormones
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...
, although in
India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
one
selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...
is marketed as a contraceptive. The original hormonal method—the
combined oral contraceptive 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: progest ...
—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.
There are two main types of hormonal contraceptive formulations: ''combined methods'' which contain 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
progestin
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 product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...
, and ''progestogen-only methods'' which contain only
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
or one of its synthetic analogues (progestins). Combined methods work by suppressing
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 ...
and thickening
cervical mucus; while progestogen-only methods reduce the frequency of ovulation, most of them rely more heavily on changes in cervical mucus. The incidence of certain side effects is different for the different formulations: for example,
breakthrough bleeding
Intermenstrual bleeding, previously known as metrorrhagia, is uterine bleeding at irregular intervals, particularly between the expected menstrual periods. It is a cause of vaginal bleeding.
In some women, menstrual spotting between periods occ ...
is much more common with progestogen-only methods. Certain serious complications occasionally caused by estrogen-containing contraceptives are not believed to be caused by progestogen-only formulations:
deep vein thrombosis
Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
is one example of this.
Medical uses
Hormonal contraception is primarily used for the prevention of
pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
, but is also prescribed for the treatment of
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 ...
, menstrual disorders such as
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 ...
and
menorrhagia
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding
Abnormal uterine bleeding (AUB), also known as (AVB) or as atypical ...
, and
hirsutism
Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
.
Polycystic ovary syndrome
Hormonal treatments, such as hormonal contraceptives, are frequently successful at alleviating symptoms associated with
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 ...
.
Birth control pills Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control.
Female
Two types of female oral contraceptive pill, taken once per day, are widely available:
* The combin ...
are often prescribed to reverse the effects of excessive
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
levels, and decrease ovarian hormone production.
Dysmenorrhea
Hormonal birth control methods such as
birth control pills Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control.
Female
Two types of female oral contraceptive pill, taken once per day, are widely available:
* The combin ...
, the
contraceptive patch,
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 ...
,
contraceptive implant
A contraceptive implant is an implantable medical device used for the purpose of birth control. The implant may depend on the timed release of hormones to hinder ovulation or sperm development, the ability of copper to act as a natural spermici ...
, and
hormonal IUD
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel ...
are used to treat cramping and pain associated with primary
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 ...
.
Menorrhagia
Oral contraceptives Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control.
Female
Two types of female oral contraceptive pill, taken once per day, are widely available:
* The combin ...
are prescribed in the treatment of
menorrhagia
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding
Abnormal uterine bleeding (AUB), also known as (AVB) or as atypical ...
to help regulate menstrual cycles and prevent prolonged menstrual bleeding. The
hormonal IUD
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel ...
(
Mirena
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel int ...
) releases
levonorgestrel which thins the uterine lining, preventing excessive bleeding and loss of iron.
Hirsutism
Birth control pills are the most commonly prescribed hormonal treatment for
hirsutism
Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
, as they prevent
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 ...
and decrease
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
production by the
ovaries
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. T ...
. Additionally,
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 ...
in the pills stimulates the liver to produce more of a protein that binds to androgens and reduces their activity.
Effectiveness
Modern contraceptives using steroid hormones have ''perfect-use'' or ''method'' failure rates of less than 1% per year. The lowest failure rates are seen with the implants Jadelle and Implanon, at 0.05% per year.
According to ''Contraceptive Technology'', none of these methods has a failure rate greater than 0.3% per year.
The SERM ormeloxifene is less effective than the steroid hormone methods; studies have found a perfect-use failure rate near 2% per year.
Long-acting methods such as the implant and the IUS are user-independent methods. For user-independent methods, the ''typical'' or ''actual-use'' failure rates are the same as the method failure rates.
Methods that require regular action by the user—such as taking a pill every day—have typical failure rates higher than perfect-use failure rates. ''Contraceptive Technology'' reports a typical failure rate of 3% per year for the injection Depo-Provera, and 8% per year for most other user-dependent hormonal methods.
While no large studies have been done, it is hoped that newer methods which require less frequent action (such as the patch) will result in higher user compliance and therefore lower typical failure rates.
Currently there is little evidence that there is an association between being overweight and the effectiveness of hormonal contraceptives.
Combined vs. progestogen-only
While unpredictable
breakthrough bleeding
Intermenstrual bleeding, previously known as metrorrhagia, is uterine bleeding at irregular intervals, particularly between the expected menstrual periods. It is a cause of vaginal bleeding.
In some women, menstrual spotting between periods occ ...
is a possible side effect for all hormonal contraceptives, it is more common with progestogen-only formulations. Most regimens of COCPs, NuvaRing, and the contraceptive patch incorporate a placebo or break week that causes regular withdrawal bleeding. While women using combined injectable contraceptives may experience
amenorrhea
Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
(lack of periods), they typically have predictable bleeding comparable to that of women using COCPs.
Although high-quality studies are lacking,
it is believed that estrogen-containing contraceptives significantly decrease the quantity of milk in breastfeeding women.
Progestogen-only contraceptives are not believed to have this effect.
In addition, while in general the progestogen-only pill is less effective than other hormonal contraceptives, the added
contraceptive effect of breastfeeding makes it highly effective in breastfeeding women.
While combined contraceptives increase the risk for
deep vein thrombosis
Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
(DVT – blood clots), progestogen-only contraceptives are not believed to affect DVT formation.
Side effects
Cancers
* There is a mixed effect of combined hormonal contraceptives on the rates of various cancers, with the
International Agency for Research on Cancer
The International Agency for Research on Cancer (IARC; french: Centre International de Recherche sur le Cancer, CIRC) is an intergovernmental agency forming part of the World Health Organization of the United Nations.
Its role is to conduct and ...
(IARC) stating: "It was concluded that, if the reported association was causal, the excess risk for breast cancer associated with typical patterns of current use of combined oral contraceptives was very small."
and also saying that "there is also conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium":
* The (IARC) notes that "the weight of the evidence suggests a small increase in the relative risk for breast cancer among current and recent users" which following discontinuation then lessens over a period of 10 years to similar rates as women who never used them, as well as "The increase in risk for breast cancer associated with the use of combined oral contraceptives in younger women could be due to more frequent contacts with doctors"
[
* Small increases are also seen in the rates of ]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 ...
and hepatocellular (liver) tumours.
* 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 ovarian cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...
risks are approximately halved and persists for at least 10 years after cessation of use; although "sequential oral contraceptives which were removed from the consumer market in the 1970s was associated with an increased risk for endometrial cancer".
* Studies have overall not shown effects on the relative risks for colorectal, malignant melanoma or thyroid cancers.
* Information on progesterone-only pills is less extensive, due to smaller sampling sizes, but they do not appear to significantly increase the risk of breast cancer.
* Most other forms of hormonal contraception are too new for meaningful data to be available, although risks and benefits are believed to be similar for methods which use the same hormones; e.g., risks for combined-hormone patches are thought to be roughly equivalent to those for combined-hormone pills.
Cardiovascular disease
Combined oral contraceptives can increase the risk of certain types of cardiovascular disease in women with a pre-existing condition or already-heightened risk of cardiovascular disease. Smoking (for women over 35), metabolic conditions like diabetes, obesity and family history of heart disease are all risk factors which may be exacerbated by the use of certain hormonal contraceptives. Oral contraceptives have also been linked to an inflated risk of myocardial infarction, arterial thrombosis, and ischemic stroke.
Blood clots
Hormonal contraception methods are consistently linked with the risk of developing blood clots. However, the risk does vary depending on the hormone type or birth control method being used.
Depression
There is a growing body of research evidence investigating the links between hormonal contraception, and potential adverse effects on women's psychological health. Findings from a large Danish study of one million women (followed up from 2000-2013) were published in 2016, and reported that the use of hormonal contraception was associated with a statistically significant increased risk of subsequent depression, particularly amongst adolescents. Within this study, women on the progestogen-only pill in particular, were 34% more likely to be subsequently be given a first diagnosis of depression or to take anti-depressants, in comparison to those not on hormonal contraception. Similarly, in December 2010, another large cohort study in Sweden with women aged 12–30 (n=815,662) found an association between hormonal contraception and subsequent use of psychotropic drugs, particularly amongst adolescents (aged 12–19). They had women take the contraceptive of their choice for a year before recording results. The collected data indicated that 3.7% of contraceptive users have ended up getting prescribed a psychotropic drug, while the number of non-users was 2.5%. These studies highlight the need for further research into the links between hormonal contraception, and adverse effects on women's psychological health.
Mood
* The longer the duration of use of oral contraception can show a greater association with the diagnosis of alcohol dependence.
* Other studies suggest that mood swings are more than often associated with taking a contraceptive pill. Data shows that 45% of the women that take contraceptives experience mood swings.
* Contraceptive mood side effects include; depressive symptoms, frequent irritability, and decreased concentration.
* Oral contraceptives are not the only contraceptive that causes effects to mood level changes, implants do also. Studies show, Levonorgestrel (LNG) is releases into the body so rapidly that it is absorbed into the systemic circulation and is detectable in the body's plasma within 15 min after insertion of device. This is why some women experience strong hormonal side effects as this drug circulates into their bloodstream at a fast rate.
Types
There are two main classes of hormonal contraceptives: ''combined contraceptives'' contain both an estrogen and a progestin
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 product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...
, and progestogen-only contraceptives that contain only progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
or a synthetic analogue (progestin). There is also a non-hormonal contraceptive called ormeloxifene which acts on the hormonal system to prevent pregnancy.
Combined
The most popular form of hormonal contraception, is the combined oral contraceptive 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: progest ...
(COCP) known colloquially as ''the pill''. It is taken once a day, most commonly for 21 days followed by a seven-day break, although other regimens are also used. For women not using ongoing hormonal contraception, COCPs may be taken after intercourse as 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 ...
: this is known as the Yuzpe regimen The Yuzpe regimen is a method of emergency contraception that uses a combination of ethinyl estradiol and levonorgestrel. It is less effective and less commonly used than a larger dose of levonorgestrel alone, a dose of ulipristal acetate, or inser ...
. COCPs are available in a variety of formulations.
The contraceptive patch is applied to the skin and worn continuously. A series of three patches are worn for one week each, and then the user takes a one-week break. NuvaRing
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 i ...
is worn inside the vagina. A ring is worn for three weeks. After removal, the user takes a one-week break before inserting a new ring. As with COCPs, other regimens may be used with the contraceptive patch or NuvaRing to provide extended cycle combined hormonal contraception.
Some 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 ...
s can be administered as one injection per month.
Progestogen-only
The progestogen-only pill
Progestogen-only pills or progestin-only pills (POP) are contraceptive pills that contain only synthetic progestogens (progestins) and do not contain estrogen (medication), estrogen. They are colloquially known as mini pills.
Although such pills ...
(POP) is taken once per day within the same three-hour window. Several different formulations of POP are marketed. A low-dose formulation is known as ''the minipill''. Unlike COCPs, progestogen-only pills are taken every day with no breaks or placebos. For women not using ongoing hormonal contraception, progestogen-only pills may be taken after intercourse as 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 ...
. There are a number of dedicated products sold for this purpose.
Hormonal intrauterine contraceptives are known as intrauterine system
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel ...
s (IUS) or Intrauterine Devices (IUD). An IUS/IUD must be inserted by a health professional. The copper IUD does not contain hormones. While a copper-containing IUD may be used as emergency contraception, the IUS has not been studied for this purpose.
Depo Provera is an injection that provides three months of contraceptive protection. Noristerat is another injection; it is given every two months.
Contraceptive implants
A contraceptive implant is an implantable medical device used for the purpose of birth control. The implant may depend on the timed release of hormones to hinder ovulation or sperm development, the ability of copper to act as a natural spermici ...
are inserted under the skin of the upper arm, and contain progesterone only. Jadelle (Norplant 2) consists of two rods that release a low dose of hormones. It is effective for five years. Nexplanon has replaced the former Implanon
Etonogestrel is a medication which is used as a means of hormonal contraceptive, birth control for women. It is available as an implant placed under the skin of the upper arm under the brand names Nexplanon and Implanon, and in combination with ...
and is also a single rod that releases etonogestrel (similar to the body's natural progesterone). The only difference between Implanon and Nexplanon is Nexplanon is radio opaque and can be detected by x-ray. This is needed for cases of implant migration. It is effective for three years and is usually done in office. It is over 99% effective. It works in 3 ways:
1. Prevents ovulation- usually an egg does not mature
2. thickens cervical mucus so to prevent sperm from reaching the egg
3. If those 2 fail, the last is the progesterone causes the lining of the uterus to be too thin for implantation.
Ormeloxifene
Ormeloxifene is a selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...
(SERM). Marketed as Centchroman, Centron, or Saheli, it is pill that is taken once per week. Ormeloxifene is legally available only in India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
.
Mechanism of action
The effect of hormonal agents on the reproductive system is complex. It is believed that combined hormonal contraceptives work primarily by preventing ovulation and thickening cervical mucus. Progestogen-only contraceptives can also prevent ovulation, but rely more significantly on the thickening of cervical mucus. Ormeloxifene does not affect ovulation, and its mechanism of action is not well understood.
Combined
Combined hormonal contraceptives were developed to prevent 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 ...
by suppressing the release of gonadotropin
Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chorioni ...
s. They inhibit follicular development and prevent ovulation as a primary mechanism of action.[ pp. 257–258:]Mechanism of action
COCs prevent fertilization and, therefore, qualify as contraceptives. There is no significant evidence that they work after fertilization. The progestins in all COCs provide most of the contraceptive effect by suppressing ovulation and thickening cervical mucus, although the estrogens also make a small contribution to ovulation suppression. Cycle control is enhanced by the estrogen.
Because COCs so effectively suppress ovulation and block ascent of sperm into the upper genital tract, the potential impact on endometrial receptivity to implantation is almost academic. When the two primary mechanisms fail, the fact that pregnancy occurs despite the endometrial changes demonstrates that those endometrial changes do not significantly contribute to the pill's mechanism of action.
Progestogen negative feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...
decreases the pulse frequency of gonadotropin-releasing hormone
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...
(GnRH) release by the hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
, which decreases the release of 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 greatly decreases the release of luteinizing 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) by the anterior pituitary
A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
levels. Progestogen negative feedback and the lack of estrogen positive feedback
Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
on LH release prevent a mid-cycle LH surge. Inhibition of follicular development and the absence of a LH surge prevent ovulation.
Estrogen was originally included in oral contraceptives for better cycle control (to stabilize the endometrium and thereby reduce the incidence of breakthrough bleeding), but was also found to inhibit follicular development and help prevent ovulation. Estrogen negative feedback on the anterior pituitary greatly decreases the release of FSH, which inhibits follicular development and helps prevent ovulation.
Another primary mechanism of action of all progestogen-containing contraceptives is inhibition of sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
penetration through the cervix
The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
into the upper genital tract
The female reproductive system is made up of the internal and external sex organs that function in the reproduction of new offspring. In humans, the female reproductive system is immature at birth and develops to maturity at puberty to be abl ...
(uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
and fallopian tube
The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
s) by decreasing the amount of and increasing the viscosity
The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water.
Viscosity quantifies the inte ...
of the cervical mucus.
The estrogen and progestogen in combined hormonal contraceptives have other effects on the reproductive system, but these have not been shown to contribute to their contraceptive efficacy:
* Slowing tubal motility and ova transport, which may interfere with fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
.
* 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 ...
atrophy and alteration of metalloproteinase
A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myogen ...
content, which may impede sperm motility and viability, or theoretically inhibit implantation.
* Endometrial edema, which may affect implantation.
Insufficient evidence exists on whether changes in the endometrium could actually prevent implantation. The primary mechanisms of action are so effective that the possibility of fertilization during combined hormonal contraceptive use is very small. Since pregnancy occurs despite endometrial changes when the primary mechanisms of action fail, endometrial changes are unlikely to play a significant role, if any, in the observed effectiveness of combined hormonal contraceptives.
Progestogen-only
The mechanism of action of progestogen-only contraceptives depends on the 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. ...
activity and dose.
Low dose progestogen-only contraceptives include traditional progestogen-only pills, the subdermal implant Jadelle and the intrauterine system
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel ...
Mirena. These contraceptives inconsistently inhibit ovulation in ~50% of cycles and rely mainly on their progestogenic effect of thickening the cervical mucus and thereby reducing sperm viability and penetration.
Intermediate dose progestogen-only contraceptives, such as the progestogen-only pill Cerazette (or the subdermal implant Implanon
Etonogestrel is a medication which is used as a means of hormonal contraceptive, birth control for women. It is available as an implant placed under the skin of the upper arm under the brand names Nexplanon and Implanon, and in combination with ...
), allow some follicular development but much more consistently inhibit ovulation in 97–99% of cycles. The same cervical mucus changes occur as with low dose progestogens.
High dose progestogen-only contraceptives, such as the injectables Depo-Provera
Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...
and Noristerat, completely inhibit follicular development and ovulation. The same cervical mucus changes occur as with very low dose and intermediate dose progestogens.
In anovulatory cycles using progestogen-only contraceptives, the endometrium is thin and atrophic. If the endometrium was also thin and atrophic during an ovulatory cycle, this could theoretically interfere with implantation of a blastocyst (embryo).
Ormeloxifene
Ormeloxifene does not affect ovulation. It has been shown to increase the rate of blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
development and to increase the speed at which the blastocyst is moved from the fallopian tube
The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
s into the uterus. Ormeloxifene also suppresses proliferation and decidualization
Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy. This includes morphological and functional changes (the decidual reaction) to endometrial stromal cells (ESCs), ...
of the 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 ...
(the transformation of the endometrium in preparation for possible implantation of an embryo). While they are believed to prevent implantation rather than fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
, exactly how these effects operate to prevent pregnancy is not understood
Emergency contraception
The use of emergency contraceptives (ECs) allows for the prevention of a pregnancy after unprotected sex or contraception failure. In the United States, there are currently four different methods available, including ulipristal acetate (UPA), an oral progesterone receptor agonist-antagonist; levonorgestrel (LNG), an oral progestin; off-label use of combined oral contraceptives (Yuzpe regimen); and the copper intrauterine device (Cu-IUD).
Types
UPA, a progesterone agonist-antagonist, was approved by the FDA in 2010 for use as an EC. UPA acts as a partial agonist and antagonist of the progesterone receptor and works by preventing both ovulation and fertilization. Users of UPA are likely to experience delayed menses after the expected date. In the United States, UPA is sold under the brand name Ella, which is a 30 mg single pill to be taken up to 120 hours after unprotected sex. UPA has emerged as the most effective EC pill, however, the access to UPA is very limited in US cities. UPA is a prescription emergency contraceptive pill and a recent study has found that less than 10% of pharmacies indicated that a UPA prescription could be filled immediately. 72% of pharmacies reported the ability to order UPA and the prescription to be filled in a median wait time of 24 hours.
Plan B one step was the first levonorgestrel progestin-only EC approved by the FDA in 1999. Currently, there are many different brands of levonorgestrel EC pills, including Take Action, Next Choice One Dose, and My Way and regimens include a single 1.5 mg pill of levonorgestrel. Levonorgestrel EC pills should be taken up to 72 hours after unprotected sex due to the drug becoming less effective over time. Levonorgestrel acts as an agonist of the progesterone receptor, preventing ovulation. Users of levonorgestrel often experience menses before the expected date. A prescription for levonorgestrel is not needed and can be found over the counter at local pharmacies. Because levonorgestrel does not have any life-threatening side effects, it has been approved by the FDA for use by all age groups.
The Yuzpe regimen used combination oral contraceptives for EC and has been used since 1974. This regimen is no longer commonly used due to side effects such as nausea and vomiting, as well as the discovery of more effective methods. The regimen consists of two pills, each containing a minimum 100 μg of ethinyl estradiol and a minimum of 500 μg of levonorgestrel. The first pill is taken 72 hours after unprotected sex and the second pill is taken 12 hours after the first. The Yuzpe regimen is often used in areas where dedicated EC methods are unavailable or where EC is not accepted.
The most effective form of EC is the insertion of a Cu-IUD within 5 days of unprotected sex. Because the Cu-IUD is inserted into the uterus, it has the advantage of providing continued contraception for up to 10 years. Cu-IUDs have been the only IUDs that have been approved as ECs due to the mechanism in hormonal and copper IUDs differing. Hormonal IUDs are used for the treatment of unplanned pregnancies by being placed in the uterus after an oral EC has been taken.
Frequency of use
Pills—combined and progestogen-only—are the most common form of hormonal contraception. Worldwide, they account for 12% of contraceptive use. 21% of users of reversible contraceptives choose COCPs or POPs. Pills are especially popular in more developed countries, where they account for 25% of contraceptive use.[ Data from surveys 1997–2007.]
Injectable hormonal contraceptives are also used by a significant portion—about 6%—of the world's contraceptive users.[ See Table 60.] Other hormonal contraceptives are less common, accounting for less than 1% of contraceptive use.
History
In 1921, Ludwig Haberlandt
Ludwig Haberlandt (1 February 1885 – 22 July 1932) is known as a father of hormonal contraception. In 1921 he carried out experiments on rabbits and he demonstrated a temporary hormonal contraception in a female by transplanting ovaries from a se ...
demonstrated a temporary hormonal contraception in a female rabbit by transplanting ovaries from a second, pregnant, animal. By the 1930s, scientists had isolated and determined the structure of the steroid hormones
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...
and found that high doses of androgens
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
, 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 ...
s, or progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
inhibited 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 ...
. A number of economic, technological, and social obstacles had to be overcome before the development of the first hormonal contraceptive, the combined oral contraceptive 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: progest ...
(COCP). In 1957 Enovid
Mestranol/norethynodrel was the first combined oral contraceptive pill (COCP) being mestranol and norethynodrel. It sold as Enovid in the United States and as Enavid in the United Kingdom. Developed by Gregory Pincus at G. D. Searle & Company ...
, the first COCP, was approved in the United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
for the treatment of menstrual disorders. In 1960, the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
approved an application that allowed Enovid to be marketed as a contraceptive.
The first progestogen-only contraceptive was introduced in 1969: Depo-Provera
Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...
, a high-dose progestin injection. Over the next decade and a half, other types of progestogen-only contraceptive were developed: a low-dose progestogen only pill
Progestogen-only pills or progestin-only pills (POP) are contraceptive pills that contain only synthetic progestogens ( progestins) and do not contain estrogen. They are colloquially known as mini pills.
Although such pills are sometimes called ...
(1973); Progestasert, the first hormonal intrauterine device
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel ...
(1976); and Norplant
Levonorgestrel-releasing implant, sold under the brand name Jadelle among others, are devices that release levonorgestrel for birth control. It is one of the most effective forms of birth control with a one-year failure rate around 0.05%. The d ...
, the first contraceptive implant (1983).
Combined contraceptives have also been made available in a variety of forms. In the 1960s a few 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 ...
s were introduced, notably Injectable Number 1 in China
China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
and Deladroxate in Latin America
Latin America or
* french: Amérique Latine, link=no
* ht, Amerik Latin, link=no
* pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...
. A third combined injection, Cyclo-Provera, was reformulated in the 1980s by lowering the dose and renamed Cyclofem (also called Lunelle). Cyclofem and Mesigyna, another formulation developed in the 1980s, were approved by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
in 1993. NuvaRing
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 i ...
, a contraceptive vaginal ring, was first marketed in 2002. 2002 also saw the launch of Ortho Evra, the first contraceptive patch.
In 1991, ormeloxifene was introduced as a contraceptive in India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
. While it acts on the estrogen hormonal system, it is atypical in that it is a selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...
rather than an estrogen, and has the capacity for both estrogenic and antiestrogen
Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or ...
ic effects.
See also
* Reproductive Health Supplies Coalition
The Reproductive Health Supplies Coalition (RHSC) is a global partnership of public, private and non-governmental organizations. Its aim is to ensure that all people in low- and middle-income countries can choose, obtain and use the supplies and a ...
* Male hormonal contraception
Male contraceptives, also known as male birth control, are methods of preventing pregnancy that solely involve the male physiology. The most common kinds of male contraception include condoms, outercourse, and vasectomy. In domestic animals, cast ...
* Progestogen-only injectable contraceptive
Progestogen-only injectable contraceptives (POICs) are a form of hormonal contraception and progestogen-only contraception that are administered by injection and providing long-lasting birth control. As opposed to combined injectable contracepti ...
* Estradiol-containing oral contraceptive
Combined birth control pills that contain natural estradiol or an estradiol ester (e.g., estradiol valerate) include:
* Estradiol valerate and cyproterone acetate (brand name Femilar) – introduced in Finland (only) in 1993
* Estradiol valerate ...
* List of progestogens available in the United States
* List of estrogens available in the United States
References
External links
*
{{Hormonal contraceptives
Hepatotoxins
Human female endocrine system
Sex and drugs