Hormonal contraception
Encyclopedia
Hormonal contraception refers to birth control
methods that act on the endocrine system
. Almost all methods are composed of steroid hormones, although in India
one selective estrogen receptor modulator
is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive pill—was first marketed as a contraceptive in 1960. In the ensuing decades many other delivery methods have been developed, although the oral and injectable methods are by far the most popular. Altogether, 18% of the world's contraceptive users rely on hormonal methods. 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
and a progestin
, and progestogen-only methods which contain only progesterone
or one of its synthetic analogues (progestins). Combined methods work by suppressing ovulation; while progestogen-only methods reduce the frequency of ovulation, most of them rely heavily on secondary mechanisms such as changes in cervical mucus. The incidence of certain side effects is different for the different formulations: for example, breakthrough bleeding
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.
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, oestrogens or progesterone
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 (COCP). In 1957 Enovid
, the first COCP, was approved in the United States
for the treatment of menstrual disorders. In 1960, the U.S. Food and Drug Administration
approved an application that allowed Enovid to be marketed as a contraceptive.
The first progestogen-only contraceptive was introduced in 1969: Depo-Provera, 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
s were introduced, notably Injectable Number 1 in China
and Deladroxate in Latin America
. 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
in 1993. NuvaRing
, 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
. While it acts on the hormonal system, this selective estrogen receptor modulator
is not a hormone.
. Progestogen-only contraceptives contain only progesterone
or a synthetic analogue (progestin). Also marketed is ormeloxifene; while not a hormone, ormeloxifene acts on the hormonal system to prevent pregnancy.
: this is known as the Yuzpe regimen
. 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
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.
A combined injectable contraceptive
is a shot given once per month.
. There are a number of dedicated products
sold for this purpose.
Hormonal intrauterine contraceptives are known as intrauterine system
s (IUS). The only currently available brand is Mirena. An IUS must be inserted by a health professional. Mirena may be used for up to five years. While a copper-containing intrauterine device
(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.
Two types of progestogen-only contraceptive implants
are available. Both are inserted under the skin of the upper arm. Jadelle (Norplant 2) consists of two rods that release a low dose of hormones. It is effective for five years. Implanon
is a single rod that releases a moderate dose of hormones. It is effective for three years.
(SERM). Marketed as Centchroman, Centron, or Saheli, it is pill that is taken once per week. Ormeloxifene is legally available only in India
.
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.
by suppressing the release of gonadotropin
s. They inhibit follicular development
and prevent ovulation as their primary mechanism of action.
Progestagen negative feedback
decreases the pulse frequency of gonadotropin-releasing hormone
(GnRH) release by the hypothalamus
, which decreases the release of follicle-stimulating hormone
(FSH) and greatly decreases the release of luteinizing hormone
(LH) by the anterior pituitary
. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol
levels. Progestagen 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.
A secondary mechanism of action of all progestagen-containing contraceptives is inhibition of sperm
penetration through the cervix
into the upper genital tract
(uterus
and fallopian tube
s) by decreasing the amount of and increasing the viscosity
of the cervical mucus.
Other secondary mechanisms have been hypothesized. One example is endometrial
effects that prevent implantation of an embryo in the uterus. Some groups that oppose abortion consider such a mechanism to be abortifacient
, and the existence of postfertilization mechanisms is a controversial topic. Some scientists point out that the possibility of fertilization during COCP use is very small. From this, they conclude that endometrial changes are unlikely to play an important role, if any, in the observed effectiveness of COCPs. Others make more complex arguments against the existence of these mechanisms, while yet other scientists argue the existing data supports such mechanisms. The controversy is currently unresolved.
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 and the intrauterine system
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
), 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 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).
development and to increase the speed at which the blastocyst is moved from the fallopian tube
s into the uterus. Ormeloxifene also suppresses proliferation and decidualization of the endometrium
. While they are believed to prevent implantation rather than fertilization
, exactly how these effects operate to prevent pregnancy is not understood.
Injectable hormonal contraceptives are also used by a significant portion—about 6%—of the world's contraceptive users. Other hormonal contraceptives are less common, accounting for less than 1% of contraceptive use.
is a possible side effect for all hormonal contraceptives, it is significantly 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 - blot clots), progestogen-only contraceptives are not believed to affect DVT formation.
Birth control
Birth control is an umbrella term for several techniques and methods used to prevent fertilization or to interrupt pregnancy at various stages. Birth control techniques and methods include contraception , contragestion and abortion...
methods that act on the endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
. Almost all methods are composed of steroid hormones, although in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
one selective estrogen receptor modulator
Selective estrogen receptor modulator
Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively...
is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive pill—was first marketed as a contraceptive in 1960. In the ensuing decades many other delivery methods have been developed, although the oral and injectable methods are by far the most popular. Altogether, 18% of the world's contraceptive users rely on hormonal methods. 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
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
and a progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
, and progestogen-only methods which contain only progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
or one of its synthetic analogues (progestins). Combined methods work by suppressing ovulation; while progestogen-only methods reduce the frequency of ovulation, most of them rely heavily on secondary mechanisms such as changes in cervical mucus. The incidence of certain side effects is different for the different formulations: for example, breakthrough bleeding
Breakthrough bleeding
Breakthrough bleeding is an abnormal uterine bleeding that occurs between menstrual periods, especially due to irregular sloughing of the endometrium in women on combined oral contraceptives...
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
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
is one example of this.
History
In 1921, Ludwig HaberlandtLudwig Haberlandt
Ludwig Haberlandt is known as a father of the hormonal contraception. In 1921 carried out experiments on rabbits and he demonstrated a temporary hormonal contraception in a female by transplanting ovaries from a second, pregnant, animal....
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, oestrogens or progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
inhibited ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
. 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 (COCP). In 1957 Enovid
Enovid
Enovid or Enavid was the first combined oral contraceptive pill . Developed by G. D. Searle & Company, it was first made available in the U.S. in 1957. Initially Enovid was marketed only for the treatment of menstrual disorders. On May 9, 1960 the U.S...
, the first COCP, was approved in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
for the treatment of menstrual disorders. In 1960, the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approved an application that allowed Enovid to be marketed as a contraceptive.
The first progestogen-only contraceptive was introduced in 1969: Depo-Provera, 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
IntraUterine System
The IUD with progestogen, intrauterine system , or IntraUterine Contraceptive is a long-acting reversible hormonal contraceptive device that is placed in the uterus. An IUS has a hormone cylinder that releases a progestin called levonorgestrel...
(1976); and Norplant
Norplant
Norplant is a form of birth control developed by the Population Council that was first approved in 1983 in Finland, where it was manufactured by Leiras Oy Pharmaceuticals...
, 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 contraceptive
Combined injectable contraceptive monthly injection of progesterone and estradiol taken to inhibit fertility. Brand names include Cyclofem, Novafem, Mesigyna, Lunelle and Cyclo-Provera....
s were introduced, notably Injectable Number 1 in China
People's Republic of China
China , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...
and Deladroxate in Latin America
Latin America
Latin America is a region of the Americas where Romance languages – particularly Spanish and Portuguese, and variably French – are primarily spoken. Latin America has an area of approximately 21,069,500 km² , almost 3.9% of the Earth's surface or 14.1% of its land surface area...
. 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
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
in 1993. NuvaRing
NuvaRing
NuvaRing is the trade name for a combined hormonal contraceptive vaginal ring manufactured by Merck that is available by prescription...
, a contraceptive vaginal ring, was first marketed in 2002. 2002 also saw the launch of Ortho Evra, the first contraceptive patch
Contraceptive patch
A contraceptive patch is a transdermal patch applied to the skin that releases synthetic estrogen and progestin hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contraceptive pill with perfect use, and the patch may be more effective in typical use.The...
.
In 1991, ormeloxifene was introduced as a contraceptive in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
. While it acts on the hormonal system, this selective estrogen receptor modulator
Selective estrogen receptor modulator
Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively...
is not a hormone.
Types
There are two main classes of hormonal contraceptives: combined contraceptives contain both an estrogen (usually ethinyl estradiol) and a progestinProgestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
. Progestogen-only contraceptives contain only progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
or a synthetic analogue (progestin). Also marketed is ormeloxifene; while not a hormone, ormeloxifene acts on the hormonal system to prevent pregnancy.
Combined
The most popular form of hormonal contraception, the combined oral contraceptive pill is 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 contraceptionEmergency contraception
Emergency contraception , or emergency postcoital contraception, refers to birth control measures that, if taken after sexual intercourse, may prevent pregnancy.Forms of EC include:...
: this is known as the Yuzpe regimen
Yuzpe regimen
The Yuzpe Regimen is a method of emergency contraception using a combination of estrogen and progestogen hormones and started within 72 hours of sexual intercourse. It has been superseded by a progestogen-only hormonal regimen.-History:...
. COCPs are available in a variety of formulations
Oral contraceptive formulations
Oral contraceptives come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogen and synthetic progestogens , and progestogen only pills...
.
The contraceptive patch
Contraceptive patch
A contraceptive patch is a transdermal patch applied to the skin that releases synthetic estrogen and progestin hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contraceptive pill with perfect use, and the patch may be more effective in typical use.The...
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
NuvaRing
NuvaRing is the trade name for a combined hormonal contraceptive vaginal ring manufactured by Merck that is available by prescription...
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.
A combined injectable contraceptive
Combined injectable contraceptive
Combined injectable contraceptive monthly injection of progesterone and estradiol taken to inhibit fertility. Brand names include Cyclofem, Novafem, Mesigyna, Lunelle and Cyclo-Provera....
is a shot given once per month.
Progestogen-only
The progestogen only pill (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 contraceptionEmergency contraception
Emergency contraception , or emergency postcoital contraception, refers to birth control measures that, if taken after sexual intercourse, may prevent pregnancy.Forms of EC include:...
. There are a number of dedicated products
Emergency contraceptive availability by country
The following is a list of countries that allow access to dedicated-purpose emergency contraceptive pills.-Cyprus:In Cyprus EC is available over-the-counter without prescription in pharmacies.-Estonia:...
sold for this purpose.
Hormonal intrauterine contraceptives are known as intrauterine system
IntraUterine System
The IUD with progestogen, intrauterine system , or IntraUterine Contraceptive is a long-acting reversible hormonal contraceptive device that is placed in the uterus. An IUS has a hormone cylinder that releases a progestin called levonorgestrel...
s (IUS). The only currently available brand is Mirena. An IUS must be inserted by a health professional. Mirena may be used for up to five years. While a copper-containing intrauterine device
Intrauterine device
A copper IUD is a type of intrauterine device. Most IUDs have a plastic T- or U-shaped frame which is wrapped in copper wire, with the exception of Gynefix, which is a plastic string with several copper beads, affixed to the fundus of the uterus...
(IUD) may be used as emergency contraception, the IUS has not been studied for this purpose.
Depo Provera
Depo Provera
Depo-Provera is a branded progestogen-only contraceptive, depot medroxyprogesterone acetate long acting reversible hormonal contraceptive birth control drug that is injected every 3 months...
is an injection that provides three months of contraceptive protection. Noristerat is another injection; it is given every two months.
Two types of progestogen-only contraceptive implants
Implant (medicine)
An implant is a medical device manufactured to replace a missing biological structure, support a damaged biological structure, or enhance an existing biological structure. Medical implants are man-made devices, in contrast to a transplant, which is a transplanted biomedical tissue...
are available. Both are inserted under the skin of the upper arm. Jadelle (Norplant 2) consists of two rods that release a low dose of hormones. It is effective for five years. Implanon
Implanon
Implanon, made by Organon International, is a single-rod long acting reversible hormonal contraceptive subdermal implant that is inserted just under the skin of a woman's upper arm. The 4 cm by 2 mm Implanon rod contains 68 milligrams of etonogestrel which is released over a three year...
is a single rod that releases a moderate dose of hormones. It is effective for three years.
Ormeloxifene
Ormeloxifene is a selective estrogen receptor modulatorSelective estrogen receptor modulator
Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively...
(SERM). Marketed as Centchroman, Centron, or Saheli, it is pill that is taken once per week. Ormeloxifene is legally available only in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
.
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
Long Acting Reversible Contraceptive
Long-acting reversible contraceptive methods are birth control methods that provide effective contraception for an extended period of time without requiring user action.-LARC methods:Available LARC methods include:* Intrauterine device...
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.
Mechanism of action
The effect of hormonal agents on the reproductive system is complex. Overall, while secondary methods have been theorized, combined hormonal contraceptives work by preventing ovulation. Progestin-only contraceptives can also prevent ovulation, but rely significantly on secondary mechanisms such as the thickening of cervical mucus. Ormeloxifene does not affect ovulation, and its mechanism of action is not well understood.Combined
Combined hormonal contraceptives prevent ovulationOvulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
by suppressing the release of gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s. They inhibit follicular development
Follicular phase
The follicular phase is the phase of the estrous cycle, during which follicles in the ovary mature. It ends with ovulation. The main hormone controlling this stage is estradiol....
and prevent ovulation as their primary mechanism of action.
Progestagen negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
decreases the pulse frequency of gonadotropin-releasing hormone
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
(GnRH) release by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, which decreases the release of follicle-stimulating hormone
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH) and greatly decreases the release of luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(LH) by the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
levels. Progestagen negative feedback and the lack of estrogen positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...
on LH release prevent a mid-cycle
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual 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.
A secondary mechanism of action of all progestagen-containing contraceptives is inhibition of sperm
Spermatozoon
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...
penetration through the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
into the upper genital tract
Female reproductive system (human)
The female reproductive system contains two main parts: the uterus, which hosts the developing fetus, produces vaginal and uterine secretions, and passes the anatomically male person's sperm through to the fallopian tubes; and the ovaries, which produce the anatomically female person's egg cells...
(uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
and fallopian tube
Fallopian tube
The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...
s) by decreasing the amount of and increasing the viscosity
Viscosity
Viscosity is a measure of the resistance of a fluid which is being deformed by either shear or tensile stress. In everyday terms , viscosity is "thickness" or "internal friction". Thus, water is "thin", having a lower viscosity, while honey is "thick", having a higher viscosity...
of the cervical mucus.
Other secondary mechanisms have been hypothesized. One example is endometrial
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
effects that prevent implantation of an embryo in the uterus. Some groups that oppose abortion consider such a mechanism to be abortifacient
Abortifacient
An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots....
, and the existence of postfertilization mechanisms is a controversial topic. Some scientists point out that the possibility of fertilization during COCP use is very small. From this, they conclude that endometrial changes are unlikely to play an important role, if any, in the observed effectiveness of COCPs. Others make more complex arguments against the existence of these mechanisms, while yet other scientists argue the existing data supports such mechanisms. The controversy is currently unresolved.
Progestogen-only
Low dose progestogen-only contraceptives include traditional progestogen-only pills, the subdermal implant Jadelle and the intrauterine system
IntraUterine System
The IUD with progestogen, intrauterine system , or IntraUterine Contraceptive is a long-acting reversible hormonal contraceptive device that is placed in the uterus. An IUS has a hormone cylinder that releases a progestin called 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
Implanon
Implanon, made by Organon International, is a single-rod long acting reversible hormonal contraceptive subdermal implant that is inserted just under the skin of a woman's upper arm. The 4 cm by 2 mm Implanon rod contains 68 milligrams of etonogestrel which is released over a three year...
), 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 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
Anovulation
An anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...
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 blastocystBlastocyst
The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...
development and to increase the speed at which the blastocyst is moved from the fallopian tube
Fallopian tube
The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...
s into the uterus. Ormeloxifene also suppresses proliferation and decidualization of the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
. While they are believed to prevent implantation rather than fertilization
Human fertilization
Human fertilization is the union of a humanoid egg and sperm, usually occurring in the ampulla of the uterine tube. The result of this union is the production of a zygote, or fertilized egg, initiating prenatal development...
, exactly how these effects operate to prevent pregnancy is not understood.
Prevalence
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.Injectable hormonal contraceptives are also used by a significant portion—about 6%—of the world's contraceptive users. Other hormonal contraceptives are less common, accounting for less than 1% of contraceptive use.
Combined vs. progestogen-only
While unpredictable breakthrough bleedingBreakthrough bleeding
Breakthrough bleeding is an abnormal uterine bleeding that occurs between menstrual periods, especially due to irregular sloughing of the endometrium in women on combined oral contraceptives...
is a possible side effect for all hormonal contraceptives, it is significantly 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
Lactational Amenorrhea Method
The lactational amenorrhea method is a method of avoiding pregnancies which is based on the natural postnatal infertility that occurs when a woman is amenorrheic and fully breastfeeding...
makes it highly effective in breastfeeding women.
While combined contraceptives increase the risk for deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
(DVT - blot clots), progestogen-only contraceptives are not believed to affect DVT formation.
Effects on rates of cancers
- There is a mixed effect of combined hormonal contraceptives on the rates of various cancers, with the International Agency for Research on CancerInternational Agency for Research on CancerThe International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations....
(IARC) concluding that "Combined oral contraceptives are carcinogenic to humans" and said that "there is also conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium": - The (IARC) note 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.
- Small increases are also seen in the rates of cervical cancerCervical cancerCervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
and hepatocellular (liver) tumoursHepatocellular carcinomaHepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
. - EndometrialEndometrial cancerEndometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...
and ovarian cancerOvarian cancerOvarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
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.