Early Initiation and Long-Term Use of Vaginal Progesterone may Cause Gestational Diabetes Mellitus

Preterm birth (PTB) is an important cause of neonatal mortality and morbidity. Spontaneous PTB (sPTB) is the most common cause of PTB. In patients with a singleton pregnancy, progesterone treatment appears to reduce the rate of spontaneous preterm birth in those with a previous history of spontaneous preterm labor and/or cervical shortening in the current pregnancy. Progesterone therapies used for the prevention of sPTB may increase the risk of gestational diabetes mellitus (GDM) towards the end of pregnancy owing to their effects on carbohydrate metabolism.

We aimed to show the effects of vaginal progesterone use, starting time, and duration of treatment on GDM.

A retrospective cohort study was carried out in pregnant women 18 to 39 years old who came to our hospital between January 1, 2021, and August 31, 2021, and who had a 2-hour 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks of gestation. In a total of 540 patients, 68 were diagnosed with GDM based on at least one abnormal plasma glucose value at screening. The remaining 472 patients with normal plasma glucose levels were considered as the control group. The groups were compared in terms of age, parity, pre-pregnancy body mass index (BMI), smoking, gestational age, and vaginal progesterone use. Patients using vaginal progesterone with and without GDM were then compared again in terms of indications for vaginal progesterone use, initiation time of progesterone therapy, duration of progesterone use, and cervical length.

The incidence of GDM in our study group was 12.5%. Despite the use of vaginal progesterone at a higher rate in the GDM group than in the control group (23.5 vs. 13.9%; p=0.07), it was not statistically significant. When we examined patients using progesterone as a subgroup analysis, the mean time to start vaginal progesterone treatment was 19.8±2.6 (14-24), and it was significantly earlier in the GDM group (18.1±2.0 vs. 20.2±2.6; p=0.007). Initiation of vaginal progesterone before 20 weeks of gestation was statistically significantly more frequent in the GDM group than the control group (68.8 vs. 39.4%; p=0.050 OR :3.3, 95%CI: 1.0-10.8). The mean duration of vaginal progesterone use was 50.0±15.6 days (28-90) and it was longer in the GDM group (57.8±13.4 vs. 48.1±15.6; p=0.027).

Since the duration of vaginal progesterone use will be prolonged, there may be a risk of GDM, especially in patients who started vaginal progesterone before the 20th week of pregnancy. Even if the OGTT test performed between 24-28 weeks is normal, it should be kept in mind that these patients may have GDM in the later weeks of pregnancy, and repeating the OGTT test should be considered if necessary.