Progesterone/Quinestradol 2127 improve within three menstrual cycles, but can be used for as riage, but studies have suffered from various limitations.3 A sys- Promegestone (rINN) long as the patient finds it to be beneficial.3 Etamsylate has been tematic review4 found no evidence to support routine use, but Promegestona; Promégestone; Promegestonum; R-5020. 17α- used for menorrhagia, but it is less effective than NSAIDs and there was limited evidence to suggest that women with a history tranexamic acid, and is no longer recommended.1,3 of recurrent miscarriage (3 or more consecutive miscarriages) Methyl-17-propionylestra-4,9-dien-3-one. In women who require contraception, a combined oral contra- might gain some benefit. The BNF advises that progestogen Промегестон 1,3 ceptive appears to be effective, although good evidence of this prophylaxis in women with a history of recurrent miscarriage is C22H30O2 = 326.5. is actually lacking.6 It has been suggested that extended-cycle not recommended. (See also Pregnancy, above, for reports of CAS — 34184-77-5. regimens should be considered for women with menorrhagia, as hypospadias in the offspring of women given hormonal support ATC — G03DB07. there are fewer bleeding episodes per year of treatment.2 Tradi- therapy.) ATC Vet — QG03DB07. tional therapy with progestogens such as norethisterone or me- 1. Sotiriadis A, et al. Threatened miscarriage: evaluation and man- droxyprogesterone given during the luteal phase appears to be agement. BMJ 2004; 329: 152–5. 1,3,7 2. Wahabi HA, et al. Progestogen for treating threatened miscar- ineffective in women with normal ovulatory cycles, although CH3 cyclical therapy may be of benefit in anovulatory patients as it riage. Available in The Cochrane Database of Systematic Re- 2 views; Issue 3. Chichester: John Wiley; 2007 (accessed O imposes a cycle. Progestogen therapy for 21 days of the cycle 27/06/08). 1,3,7 results in a significant reduction in menstrual blood loss, but 3. Walch KT, Huber JC. Progesterone for recurrent miscarriage: H C CH is associated with adverse effects that may limit its acceptability. truth and deceptions. Best Pract Res Clin Obstet Gynaecol 2008; 3 3 Long-acting injectable progestogens, such as medroxyprogester- 22: 375–89. one acetate, reduce menstrual blood loss or induce amenorrhoea 4. Haas DM, Ramsey PS. Progestogen for preventing miscarriage. H Available in The Cochrane Database of Systematic Reviews; Is- when they are used as contraceptives. They have therefore been sue 2. Chichester: John Wiley; 2008 (accessed 27/06/08). used for menorrhagia, although specific studies for this indica- H tion are lacking.1,3 Premature labour. Recommendations have been made re- More recently, a contraceptive levonorgestrel-containing IUD garding progesterone therapy for the prevention of premature O has been shown to be very effective in reducing menstrual blood birth in women at risk of preterm delivery (see under Hydroxy- progesterone Caproate, p.2110). loss in menorrhagia.1,2 UK guidelines3 suggest that it should be Profile considered first when either hormonal or non-hormonal treat- Premenstrual syndrome. Progestogen therapy was once Promegestone is a progestogen structurally related to progester- ment is acceptable and long-term use is anticipated, although popular for premenstrual syndrome, but beneficial responses one (p.2125). It has been given orally on a cyclical basis, in doses comparative data are scanty.8 There is also some evidence that it have not been universally achieved and the theory that progester- of 125 to 500 micrograms daily, in the treatment of menstrual may be an effective alternative to surgery, but data from long- one was necessary to correct a hormone imbalance is now losing disorders and mastalgia, and as the progestogen component of term follow-up are needed.9 As there can be changes in bleeding ground (see p.2099). Progesterone has been given orally, vagi- menopausal HRT. pattern associated with this device, particularly in the first few nally, and rectally, in continuous and luteal phase regimens. cycles, use for at least 6 months is advised to enable full assess- However, systematic reviews1,2 have found no convincing evi- Preparations ment of benefit.3 dence to support its use. Proprietary Preparations (details are given in Part 3) Danazol is also effective,10 producing about a 50% reduction in 1. Wyatt K, et al. Efficacy of progesterone and progestogens in Fr.: Surgestone; Port.: Surgestone. menstrual blood loss,1 but has significant adverse effects and management of premenstrual syndrome: systematic review. BMJ treatment is usually limited to 3 to 6 months. Gonadorelin ana- 2001; 323: 776–80. 2. Ford O, et al. Progesterone for premenstrual syndrome. Availa- logues are effective for menorrhagia associated with fibroids ble in The Cochrane Database of Systematic Reviews; Issue 4. Promestriene (rINN) (p.2107).1 When used pre-operatively for endometrial thinning, Chichester: John Wiley; 2006 (accessed 27/06/08). Promestrien; Promestriène; Promestrieno; Promestrienum. 17β- they produce more consistent results than danazol.11 Gonadore- lin analogues may therefore be considered before surgery or Preparations Methoxy-3-propoxyestra-1,3,5(10)-triene. when other options for fibroids are contra-indicated, but ‘add- BP 2008: Progesterone Injection; Проместриен back’ hormone replacement is recommended for the manage- USP 31: Progesterone Injectable Suspension; Progesterone Injection; Pro- C H O = 328.5. gesterone Intrauterine Contraceptive System; Progesterone Vaginal Sup- 22 32 2 ment of adverse effects from oestrogen deficiency or if they are positories. CAS — 39219-28-8. used for more than 6 months.3 ATC — G03CA09. Proprietary Preparations (details are given in Part 3) In patients who fail to respond to drug treatment, or in whom Arg.: Crinone; Faselut†; Gester; Mafel; Progest; Proluton; Utrogestan; Aus- ATC Vet — QG03CA09. such therapy is inappropriate, various surgical options exist. tral.: Crinone; Proluton; Austria: Utrogestan; Belg.: Crinone; Progestogel; Conservative surgical techniques, where the endometrium is ab- Utrogestan; Braz.: Crinone; Evocanil; Utrogestan; Canad.: Crinone; Pro- metrium; Chile: Crinone†; Hormoral; Progendo; Progering; Cz.: Agolutin; lated or resected, are increasingly being used, and are an effective CH3 alternative to hysterectomy.3,12 Hysterectomy is the ultimate Crinone; Utrogestan; Denm.: Crinone; Fin.: Crinone; Lugesteron; Fr.: Es- O tima; Evapause†; Progestogel; Utrogestan; Ger.: Crinone; Progestogel; H C therapy, but is associated with significant morbidity. Utrogest; Gr.: Crinone; Promenorea; Utrogestan; Hong Kong: Crinone; 3 1. Roy SN, Bhattacharya S. Benefits and risks of pharmacological Cyclogest; Endometrin; Progestogel; Utrogestan; Hung.: Utrogestan; In- agents used for the treatment of menorrhagia. Drug Safety 2004; dia: Crinone; Dubagest; Naturogest; Profine†; Progest†; Remens; Uterone; 27: 75–90. Indon.: Crinone; Irl.: Crinone; Utrogestan; Israel: Crinone; Endometrin; H 2. Nelson AL, Teal SB. Medical therapies for chronic menor- Gestone; Utrogestan; Ital.: Crinone; Esolut; Lutogin†; Progeffik; Progesto- rhagia. Obstet Gynecol Surv 2007; 62: 272–81. gel†; Progestol†; Prometrium; Prontogest; Malaysia: Crinone; Cyclogest; 3. National Collaborating Centre for Women’s and Children’s Utrogestan†; Mex.: Crinone; Cuerpo Amarillo Fuerte; Gepromi; Geslutin; H H Health/NICE. Heavy menstrual bleeding (issued January 2007). Gestageno; Premastan; Prosphere; Utrogestan; Neth.: Progestan; Norw.: H3C Available at: http://www.nice.org.uk/nicemedia/pdf/ Crinone; NZ: Crinone; Gestone; Philipp.: Crinone; Pol.: Luteina; Port.: O CG44FullGuideline.pdf (accessed 27/06/08) Crinone; Progenar†; Progestogel; Utrogestan; Rus.: Crinone (Крайнон); 4. Lethaby A, et al. Nonsteroidal anti-inflammatory drugs for Progestogel (Прожестожель); Utrogestan (Утрожестан); S.Afr.: Crinone; heavy menstrual bleeding. Available in The Cochrane Database Cyclogest; Utrogestan; Singapore: Crinone; Cyclogest; Utrogestan†; Profile of Systematic Reviews; Issue 4. Chichester: John Wiley; 2007 Spain: Crinone; Darstin; Progeffik; Progestogel†; Progestosol; Utrogestan; Promestriene is a derivative of estradiol (p.2097) that has been (accessed 27/06/08). Swed.: Crinone; Switz.: Crinone; Progestogel; Utrogestan; Thai.: Crinone; used topically in menopausal atrophic vaginitis, and in sebor- 5. Lethaby A, et al. Antifibrinolytics for heavy menstrual bleed- Cyclogest; Gestone†; Progestogel; Utrogestan; Turk.: Crinone; Cyclogest; rhoea and acne. ing. Available in The Cochrane Database of Systematic Re- Progestan; UK: Crinone; Cyclogest; Gestone; Utrogestan; USA: Crinone; views; Issue 4. Chichester: John Wiley; 2000 (accessed Endometrin; Prochieve; Progestasert†; Prometrium; Venez.: Crinone; Pro- Preparations gendo; Progestogel; Utrogestan. 27/06/08). Proprietary Preparations (details are given in Part 3) 6. Iyer V, et al. Oral contraceptive pills for heavy menstrual bleed- Multi-ingredient: Arg.: Cristerona; Fempack; Hosterona; Lubriderm; Arg.: Colpotrophine; Braz.: Colpotrofine; Cz.: Colpotrophine†; Hong ing. Available in The Cochrane Database of Systematic Re- Menstrogen; Tropivag Plus; Braz.: Ginecoside†; Normomensil†; Fr.: Florg- views; Issue 2. Chichester: John Wiley; 1997 (accessed Kong: Colpotrophine; Ital.: Colpotrophine; Mex.: Colpotrophine; Port.: ynal; Synergon; Trophigil; Ger.: Jephagynon†; Ital.: Biormon†; Menovis; Colpotrophine; Singapore: Colpotrophine; Spain: Colpotrofin; Delipo- 27/06/08). Malaysia: Duogynon; Mex.: Damax; Genofort; Lutoginestryl F; Metrigen 7. Lethaby A, et al. Cyclical progestogens for heavy menstrual derm; Switz.: Colpotrophine; Turk.: Colpotrophine; Venez.: Colpotrofi- Fuerte; Ominol†; Primoson-F; Progediol†; Proger-F; Port.: Emmenovis†; na†. bleeding. Available in The Cochrane Database of Systematic Thai.: Duoton; Phenokinon-F; Turk.: Di-Pro; Synergon; Venez.: Cycloges- Reviews; Issue 1. Chichester: John Wiley; 2008 (accessed terin†; Ginecosid. Multi-ingredient: Cz.: Colposeptine†; Hong Kong: Colposeptine; 27/06/08). Port.: Trophoseptine; Turk.: Colposeptine. 8. Lethaby AE, et al. Progesterone or progestogen-releasing intra- uterine systems for heavy menstrual bleeding. Available in The Cochrane Database of Systematic Reviews; Issue 4. Chichester: Proligestone (BAN, rINN) John Wiley; 2005 (accessed 27/06/08). Quinestradol (BAN, rINN) 9. Marjoribanks J, et al. Surgery versus medical therapy for heavy Proligeston; Proligestona; Proligestoni; Proligestonum. 14a,17α- menstrual bleeding. Available in The Cochrane Database of Propylidene dioxypregn-4-ene-3,20-dione. Oestriol 3-Cyclopentyl Ether; Quinestradiol; Quinestradolum. 3- Systematic Reviews; Issue 2. Chichester: John Wiley; 2006 (ac- Cyclopentyloxyestra-1,3,5(10)-triene-16α,17β-diol. cessed 27/06/08). Пролигестон 10. Beaumont H, et al. Danazol for heavy menstrual bleeding. Хинэстрадол C24H34O4 = 386.5. Available in The Cochrane Database of Systematic Reviews; Is- C H O = 356.5. sue 3. Chichester: John Wiley; 2007 (accessed 27/06/08). CAS — 23873-85-0. 23 32 3 11. Sowter MC, et al. Pre-operative endometrial thinning agents be- ATC Vet — QG03DA90. CAS — 1169-79-5. fore endometrial destruction for heavy menstrual bleeding. Available in The Cochrane Database of Systematic Reviews; Is- sue 3. Chichester: John Wiley; 2002 (accessed 27/06/08). OCH3 OH 12. Lethaby A, et al. Endometrial resection and ablation versus hys- H3C terectomy for heavy menstrual bleeding. Available in The Co- H3C OH chrane Database of Systematic Reviews; Issue 2. Chichester: O John Wiley; 1999 (accessed 27/06/08). H Miscarriage. Threatened miscarriage is a common complica- H3C H tion of pregnancy that presents before 20 weeks of gestation as H H vaginal bleeding, with or without abdominal pain, while the cer- O H CH3 vix is closed and the fetus is viable. Endogenous progesterone is O normally produced by the corpus luteum to maintain pregnancy, O and low concentrations have been associated with pregnancy Profile loss. Progestogen therapy has therefore been widely used in the Profile Quinestradol is a synthetic oestrogen that has been given orally treatment of threatened miscarriage,1 but there is a paucity of Proligestone is a progestogen used in veterinary medicine. for the treatment of menopausal vaginal symptoms. clinical study data to support routine use.2 Similarly, pro- gestogens have been used prophylactically to prevent miscar- The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)