Algestone acetophenide, also known more commonly asdihydroxyprogesterone acetophenide (DHPA) and sold under the brand namesPerlutal andTopasel among others, is aprogestin medication which is used in combination with anestrogen as a form of long-lastinginjectable birth control.[3][4][5][6] It has also been used alone, but is no longer available as a standalone medication.[7][8][9] DHPA is not activeby mouth and is given once a month byinjection into muscle.[4][5][6]
DHPA was discovered in 1958 and was introduced for medical use in the 1960s.[14][15][16] It was not introduced in theUnited States, but it is marketed widely throughoutLatin America.[17][18][7][16] It was also previously available alone inItaly and as a combined injectable contraceptive inPortugal andSpain, but has been discontinued in these countries.[8]
75 mg DHPA and 10 mg estradiol enantate (brand name Ova Repos; discontinued)
150 mg DHPA and 10 mg estradiol benzoate butyrate (brand names Neolutin N, Redimen, Soluna, Unijab)
A 90 mg DHPA and 6 mg estradiol enantate formulation was also studied, but was never marketed.[27][28][29] The combination of DHPA and estradiol enantate has also been studied at other doses ranging from 75 to 200 mg DHPA and 5 to 50 mg estradiol enantate.[30]
Clinical studies have found that, on the basis ofendometrial changes, E2-EN/DHPA appears, at the doses used, to be an estrogen-dominant combination.[13]
An effectiveovulation-inhibiting dose of DHPA is 100 mg when given alone.[34][35]
DHPA was first described in the literature in 1958 and was patented in 1960.[14][15] It was developed in combination withestradiol enantate as a long-lastingcombined injectable contraceptive under the tentative brand names Deladroxate and Droxone bySquibb and was studied in women starting in 1964.[61][35][62][27] Development was discontinued by Squibb in theUnited States in the late 1960s due to concerns oftoxicological findings in animals, includingmammary glandtumors inbeagle dogs andpituitaryhyperplasia in rats, as well as possible accumulation of estradiol enantate in the body with continued use.[1][17][16] Subsequent research has shed doubt that these animal findings are applicable to humans and that the dosages required for contraception would pose any risks.[17][1] Although the medication was not marketed in the United States, its development was continued elsewhere and it went on to be introduced and widely used inLatin America andSpain.[18][7][16] A standalone version of DHPA was introduced inItaly in 1982 under the brand names Neolutin Depo and Neolutin Depositum.[58][7] This single-drug formulation has since been discontinued.[8][9] DHPA remains available in Latin America, but is no longer marketed inEurope.[8][9]
Algestone acetophenide are theEnglishgeneric name of the drug and itsINNMTooltip International Nonproprietary Name andUSANTooltip United States Adopted Name, whiledihydroxyprogesterone acetophenide (DHPA) is a commonly used synonym.[57][63][64][8][9][65] Its generic names in other languages are as follows:[57][63][64][8][9][65]
Portuguese andSpanish:acetofenido de algestona,algestona acetofenido,algestona acetofenida, acetofenido de dihidroxiprogesterona, anddihidroxiprogesterona acetofenido
DHPA is also known by its former developmental code nameSQ-15101.[57][7][63][64] It has been referred to asdeladroxone,droxone,alfasone acetophenide, andalphasone acetophenide as well.[57][59][58][66][67][63][64][7]
The combination of E2-EN 10 mg and DHPA 150 mg was developed under the developmental brand name Deladroxate, but this brand name was never used commercially.[26][4]
In addition to E2-EN, DHPA is marketed in combination withestradiol benzoate butyrate (EBB) as a combined injectable contraceptive under the brand names Neolutin N, Redimen, Soluna, and Unijab.[23][24][25] This combination was developed under the developmental brand name Unimens, but this brand name was never used commercially.[26][69]
In addition to E2-EN, DHPA is marketed in combination withestradiol benzoate butyrate (EBB) as a combined injectable contraceptive inPeru andSingapore.[23][24][25] EBB has a shorter duration than E2-EN of about 3 weeks and hence EBB/DHPA was developed because it was thought that it would be more suitable for use as a once-monthly combined injectable contraceptive than E2-EN/DHPA.[69]
E2-EN/DHPA is the most widely used combined injectable contraceptive in Latin America.[73] It was estimated in 1995 that E2-EN/DHPA was used as a combined injectable contraceptive in Latin America by at least 1 million women.[24] However, combined injectable contraceptives like E2-EN/DHPA are unlikely to constitute a large proportion of contraceptive use in the countries in which they are available.[24]
^abcJarquín González JD, Elda de Aguirre L, Rodríguez C, Abrego de Aguilar M, Carrillo F, León DA, et al. (September 1996). "Dihydroxyprogesterone acetophenide 150 mg + estradiol enantate 10 mg as monthly injectable contraceptives".Advances in Contraception.12 (3):213–225.doi:10.1007/BF01849664.PMID8910663.S2CID2522426.
^abcdefghijklmNewton JR, D'arcangues C, Hall PE (1994). "A review of "once-a-month" combined injectable contraceptives".Journal of Obstetrics and Gynaecology.4 (Suppl 1): S1-34.doi:10.3109/01443619409027641.PMID12290848.
^abcdLerner LJ, Brennan DM, Borman A (January 1961). "Biological activities of 16 alpha, 17 alpha dihydroxyprogesterone derivatives".Proceedings of the Society for Experimental Biology and Medicine.106:231–234.doi:10.3181/00379727-106-26296.PMID13761080.S2CID89428532.
^abcdLerner, L. J., Brennan, D. M., DePhillipo, M., & Yiacas, E. (1961). Comparison of biological activities of progesterone, norethisterone and the acetophenone derivatives of 16 alpha, 17 alpha-dihydroxyprogesterone.(Abstr.). In Federation Proceedings (Vol. 20, p. 200).
^abcdefRabe T, Runnebaum B (6 December 2012).Fertility Control — Update and Trends: Update and Trends. Springer Science & Business Media. pp. 183–.ISBN978-3-642-86696-8.Two additional monthly, combined injectable methods warrant mention. Deladroxate (commercially labelled as Perlutan, Topasel, Agurin, Horprotal and Uno-Ciclo in various countries), is a combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate, and is available in many Latin American countries and Spain. The method is highly effective, without a single pregnancy reported in large clinical trials (Koetsawang 1994). Although available since the 1960s, the method has not been studied as extensively as Cyclofem or Mesigyna. The original manufacturer withdrew support due to toxicological concerns with dihydroxyprogesterone acetophenide, and clinical evaluations continue to be published. A recent dose-finding trial compared the standard available dose of 150/10 with a lower dose of 90/6, and concluded the lower dose was equally effective (Coutinho et al., 1997).
^abcPopulation Reports: Injectables and implants. Department of Medical and Public Affairs, George Washington University. 1987. p. K-75.In the US, Squibb Pharmaceutical Company withdrew Deladroxate from clinical testing in the late 1960s because of concerns over (1) breast tumors in beagle dogs, (2) pituitary hyperplasia in rats, and (3) possible accumulation of estradiol enanthate in the body with continued use (89, 98, 243). Subsequently, however, questions have been raised about whether such animal findings are applicable to humans. Research suggests that the adverse effects of Deladroxate on animals may occur only with doses higher than the equivalent of a contraceptive dose (2, 62, 82, 121, 272).
^abKoetsawang S (April 1994). "Once-a-month injectable contraceptives: efficacy and reasons for discontinuation".Contraception.49 (4):387–398.doi:10.1016/0010-7824(94)90034-5.PMID8013221.
^Recio R, Garza-Flores J, Schiavon R, Reyes A, Diaz-Sanchez V, Valles V, et al. (June 1986). "Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive".Contraception.33 (6):579–589.doi:10.1016/0010-7824(86)90046-6.PMID3769482.
^Kawakami M, Sawyer CH (May 1967). "Effects of sex hormones and antifertility steroids in brain thresholds in the rabbit".Endocrinology.80 (5):857–871.doi:10.1210/endo-80-5-857.PMID4164655.
^Bassol S, Garza-Flores J (May 1994). "Review of ovulation return upon discontinuation of once-a-month injectable contraceptives".Contraception.49 (5):441–453.doi:10.1016/0010-7824(94)90003-5.PMID8045131.
^Henzl MR, Edwards JA (10 November 1999). "Pharmacology of Progestins: 17α-Hydroxyprogesterone Derivatives and Progestins of the First and Second Generation". In Sitruk-Ware R, Mishell DR (eds.).Progestins and Antiprogestins in Clinical Practice. Taylor & Francis. pp. 101–132.ISBN978-0-8247-8291-7.
^Becker H, Düsterberg B, Klosterhalfen H (1980). "[Bioavailability of cyproterone acetate after oral and intramuscular application in men (author's transl)]" [Bioavailability of Cyproterone Acetate after Oral and Intramuscular Application in Men].Urologia Internationalis.35 (6):381–385.doi:10.1159/000280353.PMID6452729.
^Moltz L, Haase F, Schwartz U, Hammerstein J (May 1983). "[Treatment of virilized women with intramuscular administration of cyproterone acetate]" [Efficacy of Intra muscularly Applied Cyproterone Acetate in Hyperandrogenism].Geburtshilfe und Frauenheilkunde.43 (5):281–287.doi:10.1055/s-2008-1036893.PMID6223851.
^Chu YH, Li Q, Zhao ZF (April 1986)."Pharmacokinetics of megestrol acetate in women receiving IM injection of estradiol-megestrol long-acting injectable contraceptive".The Chinese Journal of Clinical Pharmacology.The results showed that after injection the concentration of plasma MA increased rapidly. The meantime of peak plasma MA level was 3rd day, there was a linear relationship between log of plasma MA concentration and time (day) after administration in all subjects, elimination phase half-life t1/2β = 14.35 ± 9.1 days.
^abGual C, Pérez-Palacios G, Perez AE, Ruiz MR, Solis J, Cervantes A, et al. (1973). "Metabolic fate of a long-acting injectable estrogen-progestogen contraceptive".Contraception.7 (4):271–287.doi:10.1016/0010-7824(73)90145-5.ISSN0010-7824.
^Artini PG, Genazzani AR, Petraglia F (11 December 2001).Advances in Gynecological Endocrinology. CRC Press. pp. 101–.ISBN978-1-84214-071-0.Subsequently another formulation of 150 mg of dihydroxyprogesterone acetophenide (DHPA) with 10 mg estradiol enanthate (E2-EN) was tested in the 1960s3-6.
