A systematic review of dydrogesterone for the treatment of threatened miscarriage

Carp, Howard

doi:10.3109/09513590.2012.702875

Cited by 78 publications

(31 citation statements)

References 30 publications

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“…As progesterone and progestins such as dydrogesterone are frequently used as therapeutics to treat, for example recurrent pregnancy loss, 44 it is essential to clarify their exact modes of action. As progesterone and progestins such as dydrogesterone are frequently used as therapeutics to treat, for example recurrent pregnancy loss, 44 it is essential to clarify their exact modes of action.…”

Section: Discussionmentioning

confidence: 99%

“…Our recent findings improve the understanding of immunological tolerance induction by progesterone during pregnancy. As progesterone and progestins such as dydrogesterone are frequently used as therapeutics to treat, for example recurrent pregnancy loss, 44 it is essential to clarify their exact modes of action. We here propose a mechanism of progesterone-induced immunological tolerance, the selective killing of CD4 + T con cells in favor of T reg cell survival.…”

Section: Discussionmentioning

confidence: 99%

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Progesterone modulates the T‐cell response via glucocorticoid receptor‐dependent pathways

Hierweger

Engler

Friese

et al. 2019

American J Rep Immunol

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Problem Steroid hormones such as progesterone and glucocorticoids rise during pregnancy and are accountable for the adaptation of the maternal immune system to pregnancy. How steroid hormones induce fetal tolerance is not fully understood. We hypothesized that steroid hormones selectively regulate the T‐cell response by promoting T‐cell death. Method of study We incubated murine spleen cells isolated from non‐pregnant and pregnant mice with physiological concentrations of steroid hormones in vitro and analyzed T‐cell subsets after 48 h of incubation. ResultsWe found that progesterone and the synthetic glucocorticoid dexamethasone induce T‐cell death. CD4+ regulatory T (Treg) cells were refractory toward progesterone‐induced cell death, in contrast to conventional CD4+ T cells, which resulted in a preferential enrichment of CD4+ Tregcells in culture. T cells isolated from pregnant mice at early and late gestation showed comparable sensitivity to steroid‐induced cell death. The target receptor for progesterone in immune cells is controversially discussed. We provide here support of progesterone binding to the glucocorticoid receptor as only T cells lacking the glucocorticoid but not the progesterone receptor showed resistance against progesterone‐induced death. ConclusionsOur results indicate that high levels of progesterone during pregnancy can induce selective T‐cell death by binding the glucocorticoid receptor. Although physiological hormone concentrations were used, due to different bioavailability of steroid hormones in vivo these results have to be validated in an in vivo model. This mechanism might ensure immunological tolerance at the feto‐maternal interface at gestation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Progesterone modulates the T‐cell response via glucocorticoid receptor‐dependent pathways

Hierweger

Engler

Friese

et al. 2019

American J Rep Immunol

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“…In the women who were treated with vaginal progesterone, the treatment was not statistically effective in reducing miscarriage when compared to placebo (RR ¼ 0.47 95% CI, 0.17-1.30) whereas oral progestogen was effective (RR ¼ 0.54 CI 0.35-0.84). The author [29] has published a meta-analysis of five studies with 660 participants which enables a more robust conclusion of efficacy to be drawn. There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women [OR for miscarriage 0.47 (CI ¼ 0.31-0.7), 11% absolute reduction in the miscarriage rate].…”

Section: Discussionmentioning

confidence: 99%

A systematic review of dydrogesterone for the treatment of recurrent miscarriage

Carp

2015

Gynecological Endocrinology

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The objective of this systematic review was to assesses whether the orally acting progestagen, dydrogesterone lowers the incidence of subsequent miscarriage in women with recurrent miscarriage. A computerized search was performed in Medline, Embase and Ovid Medline for original reports with the product name "Duphaston" or "dydrogesterone" and limited to clinical human data. Thirteen reports of dydrogesterone treatment were identified. Two randomized trials and one non-randomized comparative trial were identified, including 509 women who fulfilled the criteria for meta-analysis. The number of subsequent miscarriages or continuing pregnancies per woman was compared in women receiving dydrogesterone compared to standard bed rest or placebo intervention. There was a 10.5% (29/275) miscarriage rate after dydrogesterone administration compared to 23.5% in control women (odds ratio for miscarriage 0.29 [confidence interval 0.13-0.65] and 13% absolute reduction in the miscarriage rate). The adverse and side effects were summarised in all 13 reports, and seemed to be minimal. Although all the predictive and confounding factors could not be controlled for, the results of this systematic review show a significant reduction of 29% in the odds for miscarriage when dydrogesterone is compared to standard care indicating a real treatment effect.

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“…Influence on nitric oxide production is another possible effect of dydrogesterone on the survival of the embryo; dydrogesterone may improve blood flow and oxygen supply in addition to maintaining a quiescent myometrium . The effective results of dydrogesterone were also reported in a previously systematic review (0.47, 95% CI = 0.31–0.7), and our conclusion strengthens the reliability of the results …”

Section: Discussionmentioning

confidence: 95%

“…30,31 The effective results of dydrogesterone were also reported in a previously systematic review (0.47, 95% CI = 0.31-0.7), and our conclusion strengthens the reliability of the results. 25 Furthermore, subgroup analysis has shown that natural progesterone has no effect on oral management (RR = 0.85, 95% CI 0.37-1.94) as well as vaginal administration (RR = 0.55, 95% CI 0.15-2.07) in the European region. Although only one article from the Asian region used natural progesterone treatment, it also suggested that natural progesterone has no effect.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of progesterone on threatened miscarriage: Difference in drug types

Wang

Luo

Bai

2019

J of Obstet and Gynaecol

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Aim To investigate whether treatment with progesterone would decrease the incidence of miscarriage in women who faced threatened miscarriage. Methods Randomized controlled trials (RCT) were identified by searching PubMed, Embase, Cochrane Library and Web of Science. Trials were included if they compared progesterone with placebo, no treatment or any other treatment given in an effort to treat threatened miscarriage. Pregnant prophylaxis drugs were not included without strict progesterone type, language and progesterone management. The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). Results Eight RCT including 845 women who faced threatened miscarriage were analyzed. Pooled data from the eight trials showed that women with threatened miscarriage who were randomized to the progesterone group had a lower risk of threatened miscarriage (RR = 0.64, 95% CI 0.48–0.85). Dydrogesterone was shown to have a lower risk of miscarriage (RR = 0.49, 95% CI 0.33–0.75) than natural progesterone (RR = 0.69, 95% CI 0.40–1.19). Oral management was demonstrated to have a lower risk of miscarriage (RR = 0.55, 95% CI 0.38–0.79) compared with vaginal administration (RR = 0.58, 95% CI 0.28–1.21). Conclusion Our findings show that progesterone agents are effective in reducing the incidence of miscarriage in threatened miscarriage. Dydrogesterone, but not natural progesterone, was associated with a lower risk of miscarriage. Given the limitations of the studies included in our meta‐analysis, it is difficult to recommend route and dose of progesterone therapy. Further head‐to‐head trials of gestational weeks and long‐time follow‐up are required.

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A systematic review of dydrogesterone for the treatment of threatened miscarriage

Cited by 78 publications

References 30 publications

Progesterone modulates the T‐cell response via glucocorticoid receptor‐dependent pathways

Progesterone modulates the T‐cell response via glucocorticoid receptor‐dependent pathways

A systematic review of dydrogesterone for the treatment of recurrent miscarriage

Efficacy of progesterone on threatened miscarriage: Difference in drug types

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