Презентация на тему Dydrogesterone versus micronized progesterone

the progesterone receptor, avoiding other receptor‑related side effects1–4
1. Schindler AE,

et al. Maturitas 2008; 61(1-2):171-180. 2. Schindler AE. Maturitas 2009; 65(Suppl 1):S3-S11. 3. Dydrogesterone CCDS. 23 June 2015. 4. Rižner TL, et al. Steroids 2011; 76(6):607-615.

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*Dydrogesterone has less pronounced anti-androgenic effects than progesterone; + effective; ± weakly effective; – not effective

progesterone receptor1
1. Schindler AE, et al. Maturitas 2008; 61(1-2):171-180.

2. Schindler AE. Maturitas 2009; 65(Suppl 1): S3-S11. 3. Dydrogesterone CCDS. 23 June 2015.

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Dydrogesterone has ~1.5 times better affinity to progesterone receptors than progesterone1

Dihydrodydrogesterone, the main metabolite of dydrogesterone, also has progestogenic activity1-3

AE, et al. Maturitas 2008; 61(1-2):171-180. 2. Schindler AE.

Maturitas 2009; 65(Suppl 1):S3-S11. 3. Stanczyk FZ, et al. Endocr Rev 2013; 34(2):171-208. 4. Patki A, Pawar VC. Gynecol Endocrinol 2007; 23(Suppl 1):68-72. 5. Ganesh A, et al. Fertil Steril 2011; 95(6):1961-1965. 6. Chakravarty BN, et al. J Steroid Biochem Mol Biol 2005; 97(5):416-420.

28%
dydrogesterone

<5% progesterone

100–300 mg
progesterone

10 mg dydrogesterone

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Oral bioavailability

Dydrogesterone requires a 10–20 times lower oral dose than micronized progesterone,1–3 providing clear clinical benefits4–6

Dydrogesterone has ~5.6 times better oral bioavailability than progesterone1–3

Oral dose

et al. Hum Reprod 1997; 12(5):1073-1079.
Dydrogesterone versus Vaginal Micronized

Progesterone Absorption and Plasma Levels

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Dydrogesterone reaches peak absorption levels more rapidly than vaginal progesterone, and these levels are maintained for a longer duration1,2

Dydrogesterone1
Has quick-effect onset (rapidly absorbed, reaching maximal levels between 30 minutes and 2.5 hours after administration)
Has a long, stable effect (mean terminal half-life is 5–7 hours)

Vaginal progesterone2
Progesterone diffuses through the entire uterus by 4–5 hours, and then decreases concentration after 5 hours
Venous blood outflow from the uterus was highest in the first 2 hours
Vaginal route permits targeted drug delivery for a short period of time

Adapted from Bulletti C, et al. Hum Reprod 1997; 12(5):1073-1079

oral and vaginal micronized progesterone are metabolized by the

liver1,2
Progesterone is associated with a risk of cholestasis in pregnancy, therefore it is only licensed in the UK for use up to Week 12 of gestation in ART/IVF and only by the vaginal route
It is estimated that more than 10 million pregnancies have been exposed to dydrogesterone. So far, there have been no indications of a harmful effect of dydrogesterone use during pregnancy3,4
A randomized controlled trial in 853 infertile women compared the efficacy and tolerability of 20 mg/day oral dydrogesterone and 90 mg 8% vaginal progesterone gel used for luteal support. Numerically more local side effects occurred in the progesterone group compared to the dydrogesterone group5

1. Utrogestan 200 mg oral capsules. SPC UK. October 2013. 2. Utrogestan 200 mg vaginal capsules. SPC UK. October 2013. 3. Queisser-Luft A. Early Hum Dev 2009; 85(6):375-377. 4. Dydrogesterone CCDS. 23 June 2015. 5. Tomic V, et al. Eur J Obstet Gynecol Reprod Biol 2015; 186:49-53.

New slide

Vaginal discharge

Vaginal bleeding

Perineal irritation

Interference with coitus

Side effects occurring at a greater frequency in the progesterone group

ART, assisted reproductive technology; IVF, in vitro fertilization

studies that compared oral versus vaginal formulations of non‑progestin

drugs, women prefer to use oral formulations than vaginal ones1,2
Application of vaginal tablets requires a private, clean room; whereas tablets can be taken orally, anywhere

1. Arvidsson C, et al. Eur J Obstet Gynecol Reprod Biol 2005; 123(1):87-91.
2. Bingham JS. Br J Vener Dis 1984; 60(3):175-177.
3. Chakravarty BN, et al. J Steroid Biochem Mol Biol 2005; 97(5):416-420.

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Vaginal discharge or irritation

Dydrogesterone group: 0%

Progesterone group: 10.5%

Satisfaction with tolerability of treatment

Dydrogesterone group: ~95%

A comparative study between dydrogesterone and vaginal micronized progesterone for luteal support3

Progesterone group: ~73%

Statistically significant difference (p<0.05)

progestogens
Is very similar to progesterone, but has enhanced oral

bioavailability2,3
Is highly selective and has a high affinity for progesterone receptors2,3
Is metabolized into compounds that are either progestogenic or inactive2,3
Has a fast onset of action and long, stable effect4
Is well tolerated and has a favorable safety profile in all approved indications, including pregnancy4–9

Note: the effectiveness and safety records of dydrogesterone are based on the body of evidence for treatment of threatened5,6,10,11 and recurrent miscarriage7

1. University of Maryland Medical Center. Complementary and Alternative Medicine Guide. Wild yam. http://umm.edu/health/medical/altmed/herb/wild-yam. 2. Schindler AE, et al. Maturitas 2009; 65(Suppl 1):S3-S11. 3. Schindler AE, et al. Maturitas 2008; 61(1-2):171-180. 4. Dydrogesterone CCDS. 23 June 2015. 5. El-Zibdeh MY, Yousef LT. Maturitas 2009; 65(Suppl 1):S43-S46. 6. Pandian RU. Maturitas 2009; 65(Suppl 1):S47-S50. 7. El-Zibdeh MY. J Steroid Biochem Mol Biol 2005; 97(5):431-434. 8. Dutta DK. Asian J Obstet Gynae Pract 2001; 5(2):3-5; 9. Queisser-Luft A. Early Hum Dev 2009; 85(6):375-377. 10. Omar MH, et al. J Steroid Biochem Mol Biol 2005; 97(5):421-425. 11. Carp H. Gynecol Endocrinol 2012; 28(12):983-990.

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