Micronized progesterone, dydrogesterone equally effective for threatened miscarriages
Both micronized progesterone (MP) and dydrogesterone (DYD) are similarly effective in treating threatened miscarriages and resolving bleeding, according to a recent Singapore study.
The prospective, parallel-group, open-label, randomized controlled trial included 118 women with threatened miscarriage who were randomly assigned to receive MP (n=59; mean age 30.7±4.1 years) or DYD (mean age 30.2±4.5 years). The mean time to follow-up was similar between the two groups (5.4±1.6 vs 5.5±1.8 days). [Eur J Obstet Gynecol Reprod Biol 2018;228:319-324]
The rate of miscarriage at or before 16 weeks of gestation was statistically comparable between the MP and DYD groups (10.2 percent vs 15.2 percent; p=0.581), as was the extent of completely resolved bleeding (62.7 percent for both groups).
Moreover, while more participants in the DYD group reported complete resolution, similar or reduced bleeding, the difference did not reach statistical significance (96.6 percent vs 89.7 percent; p=0.272).
In terms of side effects, DYD appeared to be superior to MP. Significantly more women in the MP vs DYD group reported drowsiness (34 vs 17; p=0.003); nominally more participants in the MP group reported giddiness (12 vs 4). In comparison, nonsignificantly more women in the DYD group reported nausea (17 vs 13) and abdominal bloating (9 vs 7).
This finding is not unexpected as it has been previously established that MP has sedative properties mediated by progesterone metabolites, said researchers, noting that individuals have different levels of sensitivities to such effects.
“MP, being a natural progesterone, may result in more drowsiness and giddiness owing to induction of higher levels of these sedating metabolites. Consideration must be granted that the complaint was self-reported, is nonspecific, and perception of drowsiness and dizziness can be highly subjective,” they added.
Subgroup analysis showed that serum progesterone concentration was predictive of pregnancy outcome, regardless of treatment. In the MP group, miscarriage was significantly more common in women with serum progesterone <35 vs ≥35 nmol/L (62.5 percent vs 2.0 percent; p<0.001). The same was true for the DYD group (<35 vs ≥35 nmol/L: 50.0 percent vs 8.2 percent; p=0.005).
Furthermore, the risk of miscarriage was confirmed to be significantly elevated in women with low vs high serum progesterone levels, regardless of treatment received (<35 vs ≥35 nmol/L; odds ratio, 23.8; 95 percent CI, 6.5–86.6; p<0.0001).
That low progesterone levels increase the risk of miscarriage despite MP or DYD administration may indicate that treatment may be futile women with this presentation, said researchers.
“Though causality cannot be established and concluded from this study, this finding can help in counselling and risk stratifying women who present with threatened miscarriage,” they added.
In the present study, eligible participants were recruited from the emergency department of the KK Women’s and Children’s Hospital in Singapore. Patients were administered either 200-mg oral MP twice daily for 2 weeks or 10-mg oral DYD twice daily for 2 weeks. Two-sided two-sample t-tests, Wilcoxon rank-sum and Fisher’s exact tests were used to compare variables between treatment groups.
Aside from highlighting the comparable efficacies of DYD and MP for threatened miscarriage, “[o]ur study also highlighted the need to focus on the subgroup of women with low serum progesterone,” said researchers.
“These women can be further risk stratified to find out if there is indeed a small proportion of these women who will benefit from progestogen treatment. This can better guide clinicians in the management of women with threatened miscarriage based on their serum progesterone levels and other risks factors identified,” they added.