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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 th ...
. Almost all methods are composed of steroid hormones, although in
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area, the List of countries and dependencies by population, second-most populous ...
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 ...
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: proges ...
—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 ac ...
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 female sex hormone progesterone in the body. A progestin is a ''synthetic'' progestogen. Pro ...
, 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 majo ...
or one of its synthetic analogues (progestins). Combined methods work by suppressing ovulation and thickening
cervical mucus 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 ...
; 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 occur ...
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 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 ...
, 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 th ...
and menorrhagia, and hirsutism.


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 combi ...
are often prescribed to reverse the effects of excessive androgen 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 combi ...
, the
contraceptive patch 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 contr ...
, vaginal ring, contraceptive implant, 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 int ...
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 th ...
.


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 combi ...
are prescribed in the treatment of menorrhagia 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 int ...
(
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, as they prevent ovulation and decrease androgen 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 ac ...
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 occur ...
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 (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 (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 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 ...
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 female sex hormone progesterone in the body. A progestin is a ''synthetic'' progestogen. Pro ...
, 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 majo ...
or a synthetic analogue (progestin). There is also a non-hormonal contraceptive called
ormeloxifene Ormeloxifene, also known as centchroman, is one of the selective estrogen receptor modulators, or SERMs, a class of medication which acts on the estrogen receptor. It is best known as a nonsteroidal oral contraceptive which is taken once pe ...
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: proges ...
(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: this is known as the Yuzpe regimen. COCPs are available in a variety of formulations. The
contraceptive patch 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 contr ...
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. They are colloquially known as mini pills. Although such pills are sometimes called " ...
(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. 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 in ...
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 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 bir ...
is an injection that provides three months of contraceptive protection. Noristerat is another injection; it is given every two months. Contraceptive implants are inserted under the skin of the upper arm, and contain progesterone only.
Jadelle 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 dev ...
(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 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 Ormeloxifene, also known as centchroman, is one of the selective estrogen receptor modulators, or SERMs, a class of medication which acts on the estrogen receptor. It is best known as a nonsteroidal oral contraceptive which is taken once pe ...
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 ...
(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 List of countries and dependencies by area, seventh-largest country by area, the List of countries and dependencies by population, second-most populous ...
.


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 by suppressing the release of gonadotropins. 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 of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by othe ...
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 hypothalamus ...
, 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, ...
(FSH) and greatly decreases the release of luteinizing hormone (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 pi ...
. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels. Progestogen negative feedback and the lack of estrogen positive feedback 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, ...
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 (
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 ...
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 o ...
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 int ...
of the
cervical mucus 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 ...
. 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. Pro ...
. * Endometrial atrophy and alteration of metalloproteinase 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 activity and dose. Low dose progestogen-only contraceptives include traditional progestogen-only pills, the subdermal implant
Jadelle 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 dev ...
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 in ...
Mirena. These contraceptives inconsistently inhibit ovulation in ~50% of cycles and rely mainly on their progestogenic effect of thickening the
cervical mucus 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 ...
and thereby reducing sperm viability and penetration. Intermediate dose progestogen-only contraceptives, such as the progestogen-only pill Cerazette (or the subdermal implant Implanon), 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 bir ...
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 th ...
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 o ...
s into the uterus. Ormeloxifene also suppresses proliferation and decidualization 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 layer ...
(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. Pro ...
, 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 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 and found that high doses of androgens,
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 ac ...
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 majo ...
inhibited ovulation. 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: proges ...
(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 Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
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 federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
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 bir ...
, 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 (1973); Progestasert, the first hormonal intrauterine device (1976); and Norplant, 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 List of countries and dependencies by population, most populous country, with a Population of China, population exceeding 1.4 billion, slig ...
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 ...
. 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 o ...
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 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 contr ...
. In 1991,
ormeloxifene Ormeloxifene, also known as centchroman, is one of the selective estrogen receptor modulators, or SERMs, a class of medication which acts on the estrogen receptor. It is best known as a nonsteroidal oral contraceptive which is taken once pe ...
was introduced as a contraceptive in
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area, the List of countries and dependencies by population, second-most populous ...
. 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 ...
rather than an estrogen, and has the capacity for both estrogenic and antiestrogenic effects.


See also

* Reproductive Health Supplies Coalition * Male hormonal contraception * Progestogen-only injectable contraceptive * Estradiol-containing oral contraceptive * List of progestogens available in the United States *
List of estrogens available in the United States This is a complete list of estrogens and formulations that are approved by the and available in the United States. Estrogens are used as hormonal contraceptives, in hormone replacement therapy, and in the treatment of gynecological disorders. E ...


References


External links

* {{Hormonal contraceptives Hepatotoxins Human female endocrine system Sex and drugs