Hormonal contraception

Hormonal contraception is primarily used for the prevention of pregnancy, but is also prescribed for the treatment of polycystic ovary syndrome, menstrual disorders such as dysmenorrhea and menorrhagia, and hirsutism. Polycystic ovary syndrome Hormonal treatments, such as hormonal contraceptives, are frequently successful at alleviating symptoms associated with polycystic ovary syndrome. Birth control pills 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, the contraceptive patch, vaginal ring, contraceptive implant, and hormonal IUD are used to treat cramping and pain associated with primary dysmenorrhea. Menorrhagia Oral contraceptives are prescribed in the treatment of menorrhagia to help regulate menstrual cycles and prevent prolonged menstrual bleeding. The hormonal IUD (Mirena) 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. Additionally, estrogen 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. 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. 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 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. 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 (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" and ovarian cancer risks are approximately halved and persists for at least 10 years after cessation of use; "sequential oral contraceptives, which were removed from the consumer market in the 1970s, were associated with an increased risk for endometrial cancer". • Studies have overall not shown effects on the relative risks for colorectal, melanoma, or thyroid cancers. • Information on progesterone-only pills is less extensive, due to smaller sampling sizes, but they do not appear to increase the risk of breast cancer significantly. • 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 that 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 a family history of heart disease are all risk factors that may be exacerbated by the use of certain hormonal contraceptives. 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. Emotional well-being Hormonal Contraceptives have not been consistently shown to affect emotional well-being negatively. Most research suggests that users do not experience meaningful changes in mood. This is true even in studies that find measurable differences in neural indicators of emotion. Some studies suggest that hormonal contraceptives may have small effects on specific aspects of well-being and that individuals who are particularly sensitive to hormonal fluctuations could be at increased risk for mood-related side effects. However, findings in this field remain inconsistent. Much of this inconsistency is due to methodological challenges, including variability in natural hormonal fluctuations across the menstrual cycle and differences in menstrual cycle phase at testing. These factors make it difficult to compare between hormonal contraceptive users and naturally cycling individuals. ==Types==

There are two main classes of hormonal contraceptives: combined contraceptives contain both an estrogen and a progestin, and progestogen-only contraceptives that contain only progesterone 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 (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 is applied to the skin and worn continuously. A series of three patches is 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. Some combined injectable contraceptives can be administered as one injection 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 contraception. There are several dedicated products sold for this purpose. Hormonal intrauterine contraceptives are known as intrauterine systems (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 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 and is also a single rod that releases etonogestrel (similar to the body's natural progesterone). The only difference between Implanon and Nexplanon is that 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 the office. It is over 99% effective. It works in 3 ways: 1. Prevents ovulation- usually, an egg does not mature 2. thickens cervical mucus to prevent sperm from reaching the egg 3. If those 2 fail, the last is that progesterone causes the lining of the uterus to be too thin for implantation. Ormeloxifene Ormeloxifene is a selective estrogen receptor modulator (SERM). Marketed as Centchroman, Centron, or Saheli, it is a pill that is taken once per week. Ormeloxifene is legally available only in India. ==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. Progestogen 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 FSH levels 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. While they are believed to prevent implantation rather than fertilization, 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. 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. Because levonorgestrel does not have any life-threatening side effects, it has been approved by the FDA for use by all age groups. The most effective form of EC is the insertion of a Cu-IUD within 5 days of unprotected sex. 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. 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. ==History==

Leo Loeb showed in 1911 that removing the corpora lutea hastened the next ovulation. In 1921, Ludwig Haberlandt demonstrated a temporary hormonal contraception in a female rabbit by transplanting ovaries from a second, pregnant, animal. (Makepeace et al, 1937) showed specifically that injecting progesterone inhibited ovulation in rabbits. By the 1930s, scientists had isolated and determined the structure of the steroid hormones and found that high doses of androgens, estrogens, or progesterone inhibited ovulation. Several 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, the first COCP, Enovid, 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 contraceptives 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 estrogen hormonal system, it is atypical in that it is a selective estrogen receptor modulator rather than an estrogen. It has the capacity for both estrogenic and antiestrogenic effects. == See also ==