Ethinylestradiol/cyproterone acetate (EE/CPA), also known as co-cyprindiol and sold under the brand names Diane and Diane-35 among others, is a combination of ethinylestradiol (EE), an estrogen, and cyproterone acetate (CPA), a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

and antiandrogen, which is used as a birth control pill to prevent pregnancy in women.https://www.bayer.ca/omr/online/diane-35-pm-en.pdf It is also used to treat androgen-dependent conditions in women such as acne,

seborrhea A sebaceous gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur in the greatest numbe ...

, excessive facial/body hair growth,

scalp hair loss Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...

, and high androgen levels associated with ovaries with cysts. The medication is taken by mouth once daily for 21 days, followed by a 7-day free interval.

Medical uses

EE/CPA is used as a

combined birth control 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: progesti ...

to prevent ovulation and pregnancy in women. It is also approved and used to treat androgen-dependent conditions in women such as acne,

, hirsutism,

female pattern hair loss Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...

, and hyperandrogenism due to polycystic ovary syndrome.

Available forms

EE/CPA comes in the form of oral

tablet Tablet may refer to: Medicine * Tablet (pharmacy), a mixture of pharmacological substances pressed into a small cake or bar, colloquially called a "pill" Computing * Tablet computer, a mobile computer that is primarily operated by touching the s ...

s and contains 35 or 50 μg EE and 2 mg CPA per tablet. It is taken once daily for 21 days, followed by a 7-day free interval.

Side effects

Side effects of EE/CPA include

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...

(10.2%),

breast tension Breast tension is a constellation of symptoms involving the breasts including: * Breast pain * Breast engorgement Breast engorgement occurs in the mammary glands due to expansion and pressure exerted by the synthesis and storage of breast m ...

or tenderness (6.5%),

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

(5.2%), nervousness (4.4%),

chloasma Melasma (also known as chloasma faciei,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . or the mask of pregnancy when present in pregnant women) is a tan or dark ...

(4.2%),

depressed mood Depression is a mental state of low mood and aversion to activity, which affects more than 280 million people of all ages (about 3.5% of the global population). Classified medically as a mental and behavioral disorder, the experience of ...

(3.4%), decreased libido (3.1%),

varicosities A neuroeffector junction is a site where a motor neuron releases a neurotransmitter to affect a target—non-neuronal—cell. This junction functions like a synapse. However, unlike most neurons, somatic efferent motor neurons innervate skeletal mu ...

(2.9%), nausea (1.9%),

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

(1.7%), and dizziness (1.1%). The incidence of depression with EE/CPA is the same as that with other birth control pills.

Blood clots

The risk of venous thromboembolism with EE/CPA-containing birth control pills is similar to that with EE and gestodene-, desogestrel-, and drospirenone-containing birth control pills and about 50 to 80% higher than with EE and

levonorgestrel Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand name Plan B One-Step among ...

-containing birth control pills. The absolute risk of venous thromboembolism with EE/CPA-containing birth control pills is about 1.2 to 9.9 per 10,000 women-years.

Pharmacology

EE is a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

estrogen, or an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the estrogen receptors, the biological target of estrogens like estradiol. It also has functional antiandrogenic effects by decreasing the circulating free fractions of androgens. CPA is a

(synthetic

progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

), or an agonist of the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resid ...

s, the biological target of progestogens like

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

. It also acts as an antiandrogen, or as an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...

, the biological target of androgens like testosterone and dihydrotestosterone. However, it is thought that the antiandrogenic activity of CPA may only be significant at higher doses than are present in birth control pills. Both EE and CPA have

antigonadotropic An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituita ...

effects and act as contraceptives in women by suppressing ovulation. The antigonadotropic effects of EE and CPA also contribute to the antiandrogenic efficacy of the medication by suppressing androgen production by the ovaries.

History

CPA/EE-containing birth control pills were developed by 1975 and were first introduced for medical use in 1978. They originally contained 50 μg EE (Diane); subsequently, the EE dosage was decreased to 35 μg in a new "low-dose" preparation in 1986 (Diane-35).

Society and culture

Generic names

''Co-cyprindiol'', a shortened form of ''combination of cyproterone acetate and ethinylestradiol'', is a generic name of EE/CPA. It is also known by its former developmental code names ''SHB 209 AB'' (Diane) and ''SHB 209 AE'' (Diane-35). The developmental code name SH-81041 referred to a combination of high-dose 100 mg CPA and 40–50 μg EE administered in a reverse sequential regimen.

Brand names

Brand names of EE/CPA include Diane and Diane-35, as well as Adco-Fem, Alisma, Althea, Ancea, Anuar, Avancel, Axira, Bella HEXAL, Bellgyn, Bellune, Brenda-35 ED, Chloe, Clairette, Claudia, Co-Cyprindiol, Cybelle, CyEstra-35, Cypestra-35, Cyprelle, Cyprest, Cypretil, Cypretyl, Cyproderm, Cyprodiol, Cypromix, Dafne-35, Daphne, Dialider, Diane mite, Diane-35 ED, Dianette, Diclin, Dinac, Diva-35, Dixi, Dixi-35, Drina, Elestra, Elisamylan, Elleacnelle, Erika-35, Esdian, Estelle, Estelle-35, Evashine, Evépar, Evilin, Facetix, Femina, Feminac, Feminil mite, Frauline, Giane, Giane-35, Ginet, Ginette, Gynelle, Gyneplen, Gynofen, Holgyeme, Isbela, Jennifer-35, Juliet-35 ED, Juliette, Jene, Lady-Ten, Laila-35 ED, Linface, Lunar, Manoane, Midane, Mileva, Minerva, Morea sanol, Neynna, Nortin, OC-35, Selene, Sucee, Syndi, Tess, Visofid, Vreya, Xylia, Zinnia, and Zyrona.

Availability

EE/CPA is available widely throughout the world, including in Europe,

North America North America is a continent in the Northern Hemisphere and almost entirely within the Western Hemisphere. It is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the southeast by South America and the Car ...

, South America, East Asia, South Asia, Southeast Asia, and Oceania. It is notably not available in the United States or

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

References

External links

* * {{Portal bar , Medicine Bayer brands Combined estrogen–progestogen formulations Cyproterone acetate