Oral contraceptive formulations
Encyclopedia
Oral contraceptives come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogen
and synthetic progestogens (strictly progestin
s, the term used in the United States
, but the former term is used in the United Kingdom
), and progestogen only pills (mini-pills). Combined oral contraceptive pills also come in varying types, including varying doses of estrogen, and whether the dose of estrogen or progestogen changes from week to week.
from releasing eggs (ovulation
). They also thicken the cervical mucus
, which keeps sperm
from joining with an egg
. The hormones in combination and progestogen-only pills also thin the lining of the uterus
. This could prevent pregnancy
by interfering with implantation of a blastocyst
.
Main action in typical use is prevention of ovulation.
or mestranol
(the inactive 3-methyl ether of ethinyl estradiol, which must be metabolized by the liver into the active ethinyl estradiol; 50 µg of mestranol is equivalent to only 35 µg of ethinyl estradiol and should not be used when high-dose [50 µg ethinyl estradiol] estrogen pills are needed; mestranol was the estrogen used in the first oral contraceptive, Enovid
), although in varying amounts, and one of a number of different progestogens. They are usually taken for 21 days with then a 7 day gap during which a withdrawal bleed (often, but incorrectly, referred to as a menstrual period) occurs. These differ in the amount of estrogen given, and whether they are monophasic (only one dose of estrogen and progestogen during the 21 days) or multiphasic (varying doses). The introduction of extended-cycle monophasic pills (i.e. Seasonale) has shown that the menstrual intervals can be decreased.
supplement, although some newer formulations contain more active tablets and fewer placebos. Everyday regimens (Microgynon 30 ED, Femodene ED, Logynon ED), which include seven inactive placebo pills, are rarely used in UK practice. Different formulations contain different amounts of estrogen and progestogen:
The following progestogens are used:
conditions:
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 synthetic progestogens (strictly 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...
s, the term used in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, but the former term is used in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
), and progestogen only pills (mini-pills). Combined oral contraceptive pills also come in varying types, including varying doses of estrogen, and whether the dose of estrogen or progestogen changes from week to week.
How they work
Combination pills usually work by preventing a woman's ovariesOvary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
from releasing eggs (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...
). They also thicken the cervical mucus
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...
, which keeps sperm
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
from joining with an egg
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
. The hormones in combination and progestogen-only pills also thin the lining of the 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...
. This could prevent pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
by interfering with implantation of a blastocyst
Blastocyst
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,...
.
Main action in typical use is prevention of ovulation.
Combined oral contraceptive pills
All contain an estrogen, ethinyl estradiolEthinylestradiol
Ethynylestradiol , also ethynyl estradiol , is a derivative of estradiol. Ethynyl estradiol is an orally bio-active estrogen used in almost all modern formulations of combined oral contraceptive pills...
or mestranol
Mestranol
Mestranol is the 3-methyl ether of ethinylestradiol. It was the estrogen used in many of the first oral contraceptives.It is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70% ....
(the inactive 3-methyl ether of ethinyl estradiol, which must be metabolized by the liver into the active ethinyl estradiol; 50 µg of mestranol is equivalent to only 35 µg of ethinyl estradiol and should not be used when high-dose [50 µg ethinyl estradiol] estrogen pills are needed; mestranol was the estrogen used in the first oral contraceptive, 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...
), although in varying amounts, and one of a number of different progestogens. They are usually taken for 21 days with then a 7 day gap during which a withdrawal bleed (often, but incorrectly, referred to as a menstrual period) occurs. These differ in the amount of estrogen given, and whether they are monophasic (only one dose of estrogen and progestogen during the 21 days) or multiphasic (varying doses). The introduction of extended-cycle monophasic pills (i.e. Seasonale) has shown that the menstrual intervals can be decreased.
Monophasic
These are typically given as 21 tablets of estrogen and progestogen, followed by 7 tablets of placebo or an ironIron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
supplement, although some newer formulations contain more active tablets and fewer placebos. Everyday regimens (Microgynon 30 ED, Femodene ED, Logynon ED), which include seven inactive placebo pills, are rarely used in UK practice. Different formulations contain different amounts of estrogen and progestogen:
- 15 µg ethinyl estradiol
- 60 µg gestodeneGestodeneGestodene is a progestogen hormonal contraceptive. Products containing gestodene include:*Melodene-15, Mirelle, and Minesse which contain 15 mcg of ethinylestradiol and 60 mcg of gestodene;...
— 24 days + 4 days placebo (Spain: Melodene-15 Israel:Minesse)
- 60 µg gestodene
- 20 µg ethinyl estradiol
- 1000 µg norethindrone acetateNorethindrone acetateNorethisterone acetate or norethindrone acetate is a progestin used in contraception. It is the acetate ester of norethisterone....
(UK: Loestrin 20, Galen; US: Loestrin 1/20, DuramedBarr PharmaceuticalsBarr Pharmaceuticals was a global specialty pharmaceutical company that operated in more than 30 countries worldwide. Barr were engaged in the development, manufacture and marketing of generic and proprietary pharmaceuticals, biopharmaceuticals and active pharmaceutical ingredients.-History:Barr...
; Microgestin 1/20, WatsonWatson PharmaceuticalsWatson Pharmaceuticals, Incorporated is the 5th largest pharmaceutical company in the United States based on number of prescriptions dispensed...
; Junel 1/20, Barr) - 1000 µg norethindrone acetate — 24 days + 4 days ferrous fumarateIron(II) fumarateIron fumarate, also known as ferrous fumarate, is the iron salt of fumaric acid, occurring as a reddish-orange powder, used to supplement iron intake. It has the chemical formula 424...
only (US: Loestrin 24 Fe, Warner ChilcottWarner ChilcottWarner Chilcott is a pharmaceutical company based in Rockaway, New Jersey, USA. It has production and research facilities in Fajardo, Puerto Rico, Larne, Northern Ireland, Dundalk, Ireland and Weiterstadt, Germany. It is primarily focused on two core therapeutic areas: women’s healthcare and...
) - 90 µg levonorgestrelLevonorgestrelLevonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
— continuous: 365 days/year, no placebo (US: Lybrel, WyethWyethWyeth, formerly one of the companies owned by American Home Products Corporation , was a pharmaceutical company. The company was based in Madison, New Jersey, USA...
) - 100 µg levonorgestrel (US: Alesse, Wyeth; Aviane, Barr; Lessina, Barr; Lutera, Watson; Sronyx, Watson)
- 150 µg desogestrelDesogestrelDesogestrel is a molecule used in hormonal contraceptives.-Benefits:Third-generation oral contraceptives are suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile...
(UK: Mercilon, OrganonOrganon InternationalOrganon is a human pharmaceutical company headquartered in Oss, Netherlands. In November 2007 the company became a part of Schering-Plough Corporation, acquired Organon, active pharmaceutical ingredient producer Diosynth , and its veterinary pharmaceutical sister company Intervet from Akzo Nobel. ...
) - 150 µg desogestrel — 21 days + 2 days placebo + 5 days 10 µg ethinyl estradiol only (US: Mircette, Duramed; Kariva, Barr)
- 75 µg gestodeneGestodeneGestodene is a progestogen hormonal contraceptive. Products containing gestodene include:*Melodene-15, Mirelle, and Minesse which contain 15 mcg of ethinylestradiol and 60 mcg of gestodene;...
(UK: Femodette, BayerBayerBayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
) - 3000 µg drospirenoneDrospirenoneDrospirenone is an anti-androgenic synthetic progestin that is typically used in birth control. There have been concerns raised regarding its safety and is thus not recommended as a first line agent.- Medical uses :...
— 24 days + 4 days placebo (US: Yaz, Bayer) 21 days + 7 days placebo (US: Yasminelle, Schering)
- 1000 µg norethindrone acetate
- 30 µg ethinyl estradiol
- 1500 µg norethindrone acetate (UK: Loestrin 30, Galen; US: Loestrin 1.5/30, Duramed; Microgestin 1.5/30, Watson; Junel 1.5/30, Barr)
- 300 µg norgestrelNorgestrelNorgestrel is a progestin used in hormonal contraceptives. Norgestrel is a mixture of two stereoisomers, dextro-norgestrel and levo-norgestrel . Only levonorgestrel is biologically active...
(US: Lo/Ovral, Wyeth; Low-Ogestrel, Watson; Cryselle, Barr) - 150 µg levonorgestrel (UK: Ovranette, Wyeth; Microgynon 30, Microgynon 30 ED, Bayer; US: Nordette, Duramed, Levora, Watson, Portia, Barr)
- 150 µg levonorgestrel - 21 day cycle + 7 days no pills (Canada: Min-Ovral 21)
- 150 µg levonorgestrel - 21 day cycle + 7 days placebo (Canada: Min-Ovral 28)
- 150 µg levonorgestrel — extended cycle: 84 days + 7 days placebo (US: Seasonale, Duramed; Quasense, Watson; Jolessa, Barr)
- 150 µg levonorgestrel — extended cycle: 84 days + 7 days 10 µg ethinyl estradiol only (US: Seasonique, Duramed)
- 150 µg desogestrel (UK: Marvelon, Organon; US: Desogen, Organon; Ortho-Cept, Ortho-McNeil; Apri, Barr)
- 75 µg gestodene (UK: Femodene, Femodene ED, Bayer; Minulet, Wyeth)
- 3000 µg drospirenone (US: Yasmin, Bayer; Ocella, Barr; Zarah, Watson)
- 35 µg ethinyl estradiol
- 400 µg norethindrone — chewable, spearmintSpearmintMentha spicata syn. M. cordifolia is a species of mint native to much of Europe and southwest Asia, though its exact natural range is uncertain due to extensive early cultivation. It grows in wet soils...
flavor (US: Femcon Fe, Warner Chilcott) - 400 µg norethindrone (US: Ovcon 35, Warner Chilcott; Balziva, Barr)
- 500 µg norethindrone (UK: Ovysmen, Janssen-CilagJanssen-CilagJanssen-Cilag is a subsidiary of the Johnson & Johnson pharmaceutical company. The company was founded in the early 1950s by a merger between Janssen Pharmaceutica and Cilag....
; Brevinor, PfizerPfizerPfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
; US: Modicon, Ortho-McNeil; Brevicon, Watson; Nortrel 0.5/35, Barr) - 1000 µg norethindrone (UK: Norimin, Pfizer; US: Ortho-Novum 1/35, Ortho-McNeil; Norinyl 1/35, Watson; Necon, Watson; Nortrel 1/35, Barr)
- 1000 µg ethynodiol diacetateEthynodiol diacetateEthynodiol diacetate is a molecule used in hormonal contraceptives....
(US: Demulen 1/35, Pfizer; Zovia 1/35, Watson; Kelnor, Barr) - 250 µg norgestimateNorgestimateNorgestimate is a molecule used in hormonal contraceptives.Norgestimate is a form of progesterone, which is a female hormone important for the regulation of ovulation and menstruation. Norgestimate is used with estradiol , to treat the symptoms of menopause....
(UK: Cilest, Janssen-Cilag; US: Ortho Cyclen, Ortho-McNeil; MonoNessa, Watson; Sprintec, Barr) - 2000 µg cyproterone acetateCyproteroneCyproterone acetate is an antiandrogen...
— only for severe acneAcne vulgarisAcne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...
or severe hirsutismHirsutismHirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
(UK: BANBritish Approved NameA British Approved Name is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia...
of Co-cyprindiol sold as Dianette, Bayer)
- 400 µg norethindrone — chewable, spearmint
- 50 µg mestranol (equivalent to 35 µg ethinyl estradiol)
- 1000 µg norethindrone (UK: Norinyl-1, Pfizer; US: Ortho-Novum 1/50; Ortho-McNeil; Norinyl 1/50, Watson; Necon 1/50, Watson)
- 50 µg ethinyl estradiol
- 1000 µg norethindrone (US: Ovcon 50, Warner Chilcott)
- 1000 µg ethynodiol diacetate (US: Demulen 1/50, Pfizer; Zovia 1/50, Watson)
- 500 µg norgestrel (US: Ogestrel, Watson)
- 250 µg levonorgestrel (US: Nordiol, Wyeth)
Multiphasic
- 25 µg ethinyl estradiol — triphasic
- ethinyl estradiol/norgestimate combination with 7 tablets 25 µg/180 µg, 7 tablets 25 µg/215 µg, 7 tablets 25 µg/250 µg followed by 7 placebos (Ortho Tri-Cyclen Lo, Ortho-McNeil)
- ethinyl estradiol/desogestrel combination with 7 tablets 25 µg/100 µg, 7 tablets 25 µg/125 µg, 7 tablets 25 µg/150 µg, followed by 7 tablets of ferric oxide (US: Cyclessa, Organon; Velivet, Barr)
- 20/30/35 µg ethinyl estradiol — estrophasic
- ethinyl estradiol/norethindrone acetate combination with 5 tablets 20 µg/1000 µg, 7 tablets 30 µg/1000 µg, 9 tablets 35 µg/1000 µg, followed by 7 tablets of ferrous fumarate 75 mg (US: EstrostepEstrostepEstrostep is the brand name for a female combined oral contraceptive pill, distributed by Warner Chilcott.It is the first of its kind in that it is the only oral contraceptive that changes estrogen levels while keeping progestin levels constant. The estrogen doses are as follows: 20 mg for 5 days,...
Fe, Warner Chilcott)
- ethinyl estradiol/norethindrone acetate combination with 5 tablets 20 µg/1000 µg, 7 tablets 30 µg/1000 µg, 9 tablets 35 µg/1000 µg, followed by 7 tablets of ferrous fumarate 75 mg (US: Estrostep
- 30/40/30 µg ethinyl estradiol — triphasic
- ethinyl estradiol/levonorgestrel combination with 6 tablets 30 µg/50 µg, 5 tablets 40 µg/75 µg, 10 tablets 30 µg/125 µg (UK: Trinordiol, Wyeth; Logynon, Logynon ED, Bayer; US: Triphasil, Wyeth; Trivora, Watson; Enpresse, Barr)
- ethinyl estradiol/gestodene combination with 6 tablets 30 µg/50 µg, 5 tablets 40 µg/70 µg, 10 tablets 30 µg/100 µg (UK: Triadene, Bayer; Tri-Minulet, Wyeth)
- 35 µg ethinyl estradiol — triphasic
- ethinyl estradiol/norethindrone combination with 7 tablets 35 µg/500 µg, 9 tablets 35 µg/1000 µg, 5 tablets 35 µg/500 µg (UK: Synphase, Pfizer; US: Tri-Norinyl, Watson; Leena, Watson)
- ethinyl estradiol/norethindrone combination with 7 tablets 35 µg/500 µg, 7 tablets 35 µg/750 µg, 7 tablets 35 µg/1000 µg (UK: TriNovum, Janssen-Cilag; US: Ortho-Novum 7/7/7, Ortho-McNeil; Necon 7/7/7, Watson; Nortrel 7/7/7, Barr)
- ethinyl estradiol/norgestimate combination with 7 tablets 35 µg/180 µg, 7 tablets 35 µg/215 µg, 7 tablets 35 µg/250 µg followed by 7 placebos (Ortho Tri-Cyclen, Ortho-McNeil; TriNessa, Watson; Tri-Sprintec, Barr)
- 35 µg ethinyl estradiol — biphasic
- ethinyl estradiol/norethindrone combination with 10 tablets 35 µg/500 µg, 11 tablets 35 µg/1000 µg, followed by 7 placebos (US: Ortho-Novum 10/11, Ortho-McNeil; Necon 10/11, Watson)
- ethinyl estradiol/norethindrone combination with 7 tablets 35 µg/500 µg, 14 tablets 35 µg/1000 µg (UK: BiNovum, Janssen-Cilag)
- 3/2/1 mg estradiol valerate - estrophasic
- estradiol valerate/dienogestDienogestDienogest is an orally active synthetic progesterone . It is available for use as an oral contraceptive in combination with ethinylestradiol. It has antiandrogenic activity and as a result can improve androgenic symptoms. It is a non-ethinylated progestin which is structurally related to testosterone...
combination with 2 tablets 3 mg/0 mg, followed by 5 tablets 2 mg/2 mg, 17 tablets 2 mg/3 mg, 2 tablets 1 mg/0 mg, and 2 placebos. (US: Natazia, Bayer; EU: Qlaira, Bayer Schering)
- estradiol valerate/dienogest
Progestogen only pills
Progestogen only pills (POPs) use progestogen alone with doses taken continuously and no gap between packs taken. Women may experience irregular light bleeds on POPs, and whilst irregular in the first few months of taking, usually settles to a regular pattern in time.The following progestogens are used:
- 350 µg norethindrone (UK: Micronor, Janssen-Cilag; Noriday, Pfizer; US: Micronor, Ortho-McNeil; Nor-QD, Watson; Nora-BE, Watson; Jolivette, Watson; Camila, Barr; Errin, Barr)
- 500 µg ethynodiol diacetateEthynodiol diacetateEthynodiol diacetate is a molecule used in hormonal contraceptives....
(UK: Femulen, Pfizer) - 30 µg levonorgestrelLevonorgestrelLevonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
(UK: Norgeston, Bayer; AUS: Microlut, Bayer) - 75 µg desogestrelDesogestrelDesogestrel is a molecule used in hormonal contraceptives.-Benefits:Third-generation oral contraceptives are suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile...
(UK: Cerazette, Loestrin)
Contraindication
Oral contraceptives should not be used in women who currently have the followingconditions:
- Thrombophlebitis or thromboembolic disorders
- A past history of deep vein thrombophlebitis or thromboembolic disorders
- Cerebrovascular or coronary artery disease (current or history)
- Valvular heart disease with thrombogenic complications
- Severe hypertension
- Diabetes with vascular involvement
- Headaches with focal neurological symptoms
- Major surgery with prolonged immobilization
- Known or suspected carcinoma of the breast or personal history of breast cancer
- Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
- Undiagnosed abnormal genital bleeding
- Cholestatic jaundice of pregnancy or jaundice with prior pill use
- Hepatic adenomas or carcinomas, or active liver disease
- Known or suspected pregnancy
- Hypersensitivity to any component of this product