Combined injectable birth control

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Combined injectable birth control
Background
TypeHormonal
First useAbout 1980[citation needed]
Failure rates (first year)
Perfect use0–0.2%[1]
Typical use?
Usage
Duration effect1 month
User reminders?
Advantages and disadvantages
STI protectionNo
BenefitsEspecially good if poor pill compliance

Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy.

CICs are different from progestogen-only injectable contraceptives (POICs), such as depot medroxyprogesterone acetate (DMPA; brand names Depo-Provera, Depo-SubQ Provera 104) and norethisterone enantate (NETE; brand name Noristerat), which are not combined with an estrogen and are given once every two to three months instead of once a month.[2]

Hormonal contraception works primarily by preventing ovulation, but it may also thicken the cervical mucus inhibiting sperm penetration.[3][4][5] Hormonal contraceptives also have effects on the endometrium,[6][7] that theoretically could affect implantation,[8][9][10][11]

Medical uses[edit]

CICs are administered by intramuscular injection into the deltoid, gluteus maximus, or anterior thigh.[1] They are ideally administered every 28 to 30 days, though they have been demonstrated to be effective up to 33 days.[1]

Some CICs have been said to be used by transgender women as a means of feminizing hormone therapy as well.[12]

Available forms[edit]

A variety of different CICs, generally containing a short-acting natural estradiol ester and a long-acting progestin ester, are available for clinical use.[13][14][2][15][16] Estrogens that are used include estradiol valerate, estradiol cypionate, estradiol enantate, estradiol benzoate butyrate, and estradiol, while progestins that are used include norethisterone enantate, medroxyprogesterone acetate, algestone acetophenide (dihydroxyprogesterone acetophenide), hydroxyprogesterone caproate, and megestrol acetate.[14][2][15][16] Estradiol benzoate has a duration that is too short for once-monthly CICs, and is not used in them.[17] Conversely, estradiol enantate is said to have a duration that is too long for once-monthly CICs, but is nonetheless used in them.[17]

Combined injectable contraceptives marketed for clinical use

Composition Dose Vehicle Brand Names Availability
Estradiol valerate
Norethisterone enantate
5 mg
50 mg
Oil solution Chinese Injectable No. 3, Efectimes, Ginediol, Mesigyna, Mesilar, Meslart, Mesocept, Mesygest, Nofertyl, Nofertyl Lafrancol, Noregyna, Norestrin, Norifam, Norigynon, Nostidyn, Sexseg, Solouna Approved in at least 36 countries, including Argentina, the Bahamas, Barbados, Bolivia, Brazil, Chile, Colombia, Costa Rica, the Dominican Republic, Ecuador, Egypt, El Salvador, Ghana, Grenada, Guatemala, Guyana, Haiti, Honduras, Jamaica, Kenya, Mexico, Nicaragua, Panama, Paraguay, Peru, St. Lucia, Turkey, Uruguay, Venezuela, and Zimbabwe
Estradiol cypionate
Medroxyprogesterone acetate
5 mg
25 mg
Microcrystalline aqueous suspension Ciclofem, Ciclofemina, Cyclofem, Cyclofemina, Cyclogeston, Femelin, Femydrol, Gestin, Harmonis, Lunella, Lunelle, Novafem Approved in at least 18 countries, including Bolivia, Brazil, Chile, China, Colombia, Costa Rica, El Salvador, Guatemala, Hong Kong, Indonesia, Malaysia, Mexico, Panama, Peru, Puerto Rico, Thailand, the United States, and Zimbabwe
Estradiol enantate
Algestone acetophenide
a
10 mg
150 mg
Oil solution Acefil, Agurin, Atrimon, Ciclomes, Ciclovar, Ciclovular, Cicnor, Clinomin, Cycloven, Daiva, Damix, Deladroxate§, Deprans, Deproxone, Exuna, Ginestest, Ginoplan, Gynomes, Horprotal, Listen, Luvonal, Neogestar, Neolutin, Nomagest, Nonestrol, Normagest, Normensil, Novular, Oterol, Ovoginal, Patector, Patectro, Perludil, Perlumes, Perlutal, Perlutale, Perlutan, Perlutin, Perlutin-Unifarma, Permisil, Preg-Less, Pregnolan, Progestrol, Protegin, Proter, Seguralmes, Synovular, Topasel, Unigalen, Uno-Ciclo, Vagital Approved in at least 19 countries, including Argentina, Belize, Brazil, Chile, Colombia, Costa Rica, the Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Mexico, Nicaragua, Panama, Paraguay, Peru, Portugal, and Spain
5 mg
75 mg
Oil solution Anafertin, Patector NF, Yectames Approved at least 9 countries, including Costa Rica, the Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, and Spain
10 mg
120 mg
Oil solution Unalmes, Yectuna Approved in at least 3 countries, including Brazil, Chile, and Paraguay
10 mg
75 mg
Oil solution Ova Repos Discontinued
Estradiol benzoate butyrate
Algestone acetophenide
10 mg
150 mg
Oil solution? Redimen, Soluna, Unijab, Unimens§ Approved in Peru and Singapore
Estradiol valerate
Hydroxyprogesterone caproate
5 mg
250 mg
Oil solution Chinese Injectable No. 1 Approved in China
Estradiol
Megestrol acetate
3.5 mg
25 mg
Microcrystalline aqueous suspension with a defined particle size range Chinese Injectable No. 2, Mego-E Approved in China
Notes: All are given by intramuscular injection once a month. Footnotes: = Discontinued. § = Never marketed. a = Unsorted brand names (doses unknown; for E2-EN/DHPA): Evitas, Femineo, and Primyfar. Sources:[18][2][19][14][15][20][21][22][23][24][25]

Side effects[edit]

The most prominent side effects of CICs are menstrual irregularities during the first 3 to 6 months of use.[1]

Pharmacology[edit]

Idealized curves of estradiol levels over a period of 30 days after injection of different estradiol esters in women.[15] Four data points were used to generate the curves (day 0, peak day, a third day, and day 30).[15] The measurements from which the points were drawn were taken at 24-hour intervals.[15] The estradiol esters were given mostly as combined injectable contraceptives together with a progestin.[15]

CICs contain an estrogen and a progestin. The estrogen is generally a short-acting estradiol ester, which acts as a prodrug of estradiol.[13] Esters of estradiol are natural and bioidentical estrogens, and are believed to have more favorable effects on lipid metabolism, cardiovascular health, and hemostasis than synthetic estrogens such as ethinylestradiol.[26][27][28] The progestin is a long-acting progestogen ester, which may or may not act as a prodrug.[13] Progesterone derivatives including medroxyprogesterone acetate, algestone acetophenide (dihydroxyprogesterone acetophenide), hydroxyprogesterone caproate, and megestrol acetate are active themselves and are not prodrugs, whereas the testosterone derivative norethisterone enantate is a prodrug of norethisterone. Regardless of whether they are prodrugs or not, steroid esters form a depot and have an extended duration of action due to a depot effect when administered by intramuscular or subcutaneous injection.

Because CICs are administered parenterally, they bypass the first-pass effect in the liver and intestines that occurs with oral administration of estrogens.[13] However, is estimated that about 20% of an administered dose does still eventually pass through the liver.[13] Hence, these preparations are not completely liver-neutral.[13] Nonetheless, they have dramatically reduced hepatic effects relative to oral ethinylestradiol.[29] In addition, parenteral estradiol in general has about 4- or 5-fold reduced potency in the liver than oral estradiol.[29]

History[edit]

Two CICs were introduced for clinical use by 1976: estradiol enantate/algestone acetophenide (E2-EN/DHPA; brand names Perlutan, Topasel) in Spain and Latin America, and estradiol valerate/hydroxyprogesterone caproate (EV/OHPC; brand name Injectable No. 1) in China.[30] These CICs have been described as first-generation CICs.[30] Two second-generation CICs, estradiol cypionate/medroxyprogesterone acetate (EC/MPA; brand names Cyclofem and later Lunelle) and estradiol valerate/norethisterone enantate (EV/NETE; brand name Mesigyna), were introduced for clinical use in 1993.[31][32][14]

United States[edit]

Society and culture[edit]

Availability[edit]

Known availability of CICs in countries throughout the world (as of September 2018).

CICs are available in many countries throughout the world, including widely throughout Central and South America, in Mexico and the Caribbean, in China, in several Southeast Asian and African countries, and in Turkey.[23][24][25][16][2][32][14][15][33] They were also previously available in the United States, Portugal, and Spain, but have been discontinued in these countries.[24][25]

Research[edit]

Many other CICs have been studied but have not been approved or marketed for clinical use.[14][15][34][17][35][2]

The following are marketed CICs at different doses than those that are approved:

The half-progestin-dose formulation of estradiol valerate/norethisterone enantate (5 mg / 25 mg) is also known as HRP-103 and the half-progestin-dose formulation of estradiol cypionate/medroxyprogesterone acetate (5 mg / 12.5 mg) is also known as HRP-113.[36]

The following are CICs that have never been marketed:

See also[edit]

References[edit]

  1. ^ a b c d e "FDA Approves Combined Monthly Injectable Contraceptive". Contraception Report. 12 (3). 2001. Archived from the original on September 26, 2006.
  2. ^ a b c d e f g Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S (2014). "Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control" (PDF). World J Pharm Pharm Sci. 3 (10): 364–392. ISSN 2278-4357.
  3. ^ Tamara Callahan MD , Aaron Caughey MD , Blueprints Obstetrics and Gynecology, 2013
  4. ^ KD Tripathi , Essentials of Medical Pharmacology, 2013
  5. ^ Dc Dutta's Textbook of Obstetrics, 2014
  6. ^ K. A. Petrie, A. H. Torgal, C. L. Westhoff, Matched-pairs analysis of ovarian suppressionduring oral vs. vaginal hormonal contraceptive use, „Contraception” 2011, t. 84, p. e2-3
  7. ^ R. L. Birtch, O. A. Olatunbosum, R. A. Pierson, Ovarian follicular dynamics during conventional vs continuous oral contraceptive use, „Contraception” 2006, t. 73, p. 235. p. 239.
  8. ^ K. Bugge, K. S. Richter, J. Bromer, et al., Pregnancy rates following in vitro fertilization are reduced with a thin endometrium, but are unrelated to endometrial thickness above 10 millimeters,„Fertility and Sterility” 2004, t. 82, p. S199.
  9. ^ T. Fiumino, A. Kuwata, A. Teranischi et al., Significance of endometrium thickness to evaluate endometrial receptivity for embryos in natural cycle, „Fertility and Sterility” 2008, t. 90,p. S159.
  10. ^ K. S. Richter, K. R. Bugge, J. G. Bromer, Relationship between endometrial thickness and embryo implantation, based on 1. 294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos, „Fertility and Sterility” 2007, t. 87, p. 53.
  11. ^ Rivera R, Yacobson I, Grimes D (1999). "The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices". Am J Obstet Gynecol. 181 (5 Pt 1): 1263–9. doi:10.1016/S0002-9378(99)70120-1. PMID 10561657.
  12. ^ Don Kulick (12 January 2009). Travesti: Sex, Gender, and Culture among Brazilian Transgendered Prostitutes. University of Chicago Press. pp. 64–66. ISBN 978-0-226-46101-4.
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  19. ^ Pramilla Senanayake; Malcolm Potts (14 April 2008). Atlas of Contraception, Second Edition. CRC Press. pp. 50–. ISBN 978-0-203-34732-4.
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  23. ^ a b https://www.drugs.com/international/
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Further reading[edit]