The chemical structure of dydrogesterone is very similar to progesterone, with high bioactivity when taken orally, showing high selectivity for progesterone receptors. Progesterone belongs to a natural progesterone present in the body, mainly secreted by the ovaries.
Dydrogesterone is currently the most functionally and structurally similar oral progesterone among synthetic progestogens, belonging to retrograde progesterone. Its molecular structure is different from that of natural progesterone and can be extracted from plants or synthesized artificially.
Currently, dydrogesterone has been widely used in China for the treatment of threatened miscarriage or habitual miscarriage caused by insufficient endogenous progesterone. It is said that a single tree does not make a forest; the combination of dydrogesterone with related medications can further improve efficacy. Therefore, Kangxun Network has compiled drug combinations that enhance the fetal protective effect of dydrogesterone for reference by clinical doctors.
1. Dydrogesterone + Progesterone
There was a small-scale clinical controlled study in which patients with luteal insufficiency threatened miscarriage were divided into two groups: one group received progesterone injection alone, while the other group received combined progesterone injection and oral dydrogesterone.
The results showed that although both groups showed improvement in pregnancy indicators, the combined group had better results (94% vs. 81%), and adverse reactions such as dizziness, induration, nausea, and fatigue were milder.
Therefore, both in terms of effectiveness and safety, the use of dydrogesterone in combination with progesterone is recommended for treatment, which can also effectively reduce the incidence of adverse reactions.
2. Dydrogesterone + Human Chorionic Gonadotropin (HCG) Injection
Progesterone and human chorionic gonadotropin (HCG) injection are also a good combination, with many patients believing that HCG injections alone can promote embryo growth, which is almost impossible. Clinical doctors must explain to patients that although they are both HCG, they do not simply add up.
The combination of dydrogesterone and HCG injections is to “confuse” the pituitary gland’s “hearing and vision,” making it think it is secreting luteinizing hormone, thereby better maintaining luteal function. This helps stabilize the local endometrial immune cell factors, optimize conditions for implantation, and accelerate embryo growth.
A small-scale clinical controlled trial compared HCG combined with progesterone and HCG combined with dydrogesterone, revealing a success rate of 93.4% for dydrogesterone combined with HCG and 79.0% for progesterone combined with HCG. The results indicate that dydrogesterone combined with HCG significantly improves the efficacy for threatened miscarriage patients, with a notable reduction in symptom disappearance and hormone level recovery time.
3. Dydrogesterone + Low-molecular-weight Heparin
The combination of these two drugs is quite common in clinical practice, especially for patients with antiphospholipid syndrome.
Dydrogesterone plays a crucial coordinating role in the early immune response of pregnancy, inhibiting NK cell activity, inducing predominance of Th2 cytokines, regulating the production of asymmetric antibodies, helping the fetus evade maternal rejection of paternal antigens.
Low-molecular-weight heparin not only has anti-inflammatory effects but also effectively prevents blood clot formation, improves placental blood flow, promotes fetal growth, enhances umbilical cord blood nutrient exchange, and helps stabilize the uterine environment. A small-scale clinical controlled trial divided threatened miscarriage treatment into two groups, one using only dydrogesterone, and the other using dydrogesterone in combination with low-molecular-weight heparin.
The results showed a statistically significant difference in the time it took for clinical symptoms to improve between the two groups, with an efficacy rate of 94.87% in the combination therapy group and 76.92% in the single dydrogesterone group. The combined use of dydrogesterone and low-molecular-weight heparin can harness different mechanisms of action of the drugs, have a synergistic effect, promote hormone secretion, enhance anti-miscarriage effects, and have good safety.
4. Dydrogesterone + Methylergometrine
Methylergometrine is a drug that stabilizes the uterus and prevents uterine contractions, often considered a “sacred” drug in obstetrics and gynecology. It can not only treat threatened miscarriage, severe vomiting during pregnancy, and shorten labor, but also treat dysmenorrhea and is used in hysteroscopy and embryo transfer.
In the field of threatened miscarriage treatment, methylergometrine significantly enhances the treatment effect, significantly shortening the relief time of lower abdominal pain, alleviating lumbar back pain, disappearing vaginal bleeding, and showing the effect of uterine contractions, with a low rate of adverse reactions, ultimately achieving successful fetal protection.
A small-scale clinical controlled trial compared threatened miscarriage patients’ treatment with dydrogesterone alone and dydrogesterone combined with methylergometrine.
The treatment results showed a success rate of 90% in the combination therapy group and 66.67% in the dydrogesterone-only group, with significant differences. There were also significant differences in the relief and disappearance time of clinically relevant symptoms, with a significantly lower occurrence rate of adverse reactions in the combination therapy group.
5. Dydrogesterone + Isoxsuprine Hydrochloride
Isoxsuprine hydrochloride is a drug for preventing premature labor, effectively reducing intracellular calcium ion concentration, blocking the activity of uterine muscle contraction proteins, inhibiting the frequency and intensity of uterine smooth muscle contractions, thereby prolonging pregnancy and preventing premature labor.
A study randomly divided 96 patients with threatened miscarriage into two groups of 48 each. The control group took dydrogesterone tablets orally at 10 mg/dose, 2-3 times a day, continuously for 7 days. The observation group added isoxsuprine hydrochloride injection, with 50 mg of isoxsuprine hydrochloride dissolved in 500 ml of 5% glucose injection fluid for intravenous drip, with an initial drip rate of 5 drops/min, increasing by 5 drops/min every 10 min, reaching an appropriate drip rate of 15-30 drops/min.
During the infusion process, appropriate adjustments were made based on the specific uterine contraction situation of the patients until uterine contractions were suppressed, and continuous infusion was stopped after 1 hour. Thirty minutes before the end of the intravenous drip, isoxsuprine hydrochloride tablets (10 mg/tablet) were orally administered at a rate of 1 tablet/hour, followed by 1 tablet per 4 hours on the second day and 1 tablet per 6 hours on the third day, with continuous treatment for 7 days.
The treatment results showed that the observation group had a shorter onset time and uterine contraction disappearance time, a longer gestational age extension, a higher fetal protection success rate, and significant differences from the control group (P < 0.05). After treatment, the progesterone values of both groups were higher than before treatment, uterine artery blood flow resistance and pulsatility index were lower than before treatment, and the observed group showed a greater improvement in the above indexes, with significant differences (P < 0.05). This study's results indicate that the combination of isoxsuprine hydrochloride and dydrogesterone has a better clinical effect in threatened miscarriage patients, providing a dual treatment effect, thereby increasing the success rate of fetal protection. Note: The results of the study are for professional reference only. Please refer to specific conditions for practical considerations. References: [1] Zhu H. Efficacy analysis of dydrogesterone combined with progesterone for luteal insufficiency threatened miscarriage. China Medicine and Clinic, 2020, 20(9):1525-1527. [2] Ma J. Observational study on the efficacy of dydrogesterone combined with progesterone in treating threatened miscarriage. World's Latest Medical Information Digest (Continuous Electronic Journal), 2021, 21(3):167-168. [3] Liu Z, Zhu L. Evaluation of the effectiveness of dydrogesterone combined with progesterone on threatened miscarriage. Chinese Journal of Biochemical Drugs, 2016, (7):70-72. [4] Qin Q. The effect of dydrogesterone combined with human chorionic gonadotropin on unexplained recurrent miscarriage. Clinical Medicine, 2021, 41(8):104-106. [5] Fei L, Cao L. Application analysis of isoxsuprine hydrochloride combined with dydrogesterone in the treatment of threatened miscarriage patients. Heilongjiang Medicine, 2021, 45(17):1857-1858.
