Micronized progesterone: a beneficial new modality of treatment for Egyptian patients with hyperemesis gravidarum

ABSTRACT

Hyperemesis gravidarum [HG] is a condition of intractable vomiting during pregnancy, leading to fluid, electrolyte and acid-base imbalance, nutrition deficiency and weight loss often severe enough to require hospital admission. Theories on how pregnancy hormones could cause HG assert that patients who develop HG may be exposed to higher levels of hormones during early pregnancy. Because HG is most prevalent in weeks when both the placenta and the corpus luteum produce hormones, progesterone and HCG in particular are thought to be associated with HG. Pregnancies with iatrogenic-elevated progesterone levels, such as pregnancies with multiple corpora lutea caused by controlled ovarian stimulation [COS], or pregnancies in which progesterone is administered for luteal phase support do not exhibit an increased incidence of HG, suggesting that high progesterone levels [endogenous or exogenous] alone do not cause HG. The aim of the present study was to evaluate the therapeutic role of progesterone therapy [Utrogestan] as a new modality in the management of hyperemesis gravidarum and to compare this new modality of treatment with the conventional methods used before. Forty Egyptian pregnant women below 40 years of age who are pregnant 20 weeks and had no preconception history of any other medical illnesses. They were suffering from pernicious vomiting > 5 times per day with subjective weight loss, fluid and electrolyte imbalance and ketonuria. They were randomly divided into group I, which included 20 patients suffering from HG. These patients were managed by iv fluids [5-6 litres/day] and micronized progesterone [Utrogestan] 300-400 mg vaginally/day for two weeks. Group II included another 20 pregnant women suffering from HG who received the traditional lines of treatment of HG. A control group composed of 15 pregnant women not suffering from vomiting or weight loss was also included in the study. Routine investigations included midstream urine analysis, complete blood picture [CBC], fasting blood glucose, liver function tests [serum bilirubin, AST and ALT], kidney function tests [blood urea and serum creatinine], serum electrolytes [Na and K], and serum uric acid were also measured. Assessment of fasting serum progesterone and serum estradiol level was done. Transabdominal ultrasound examination was carried out in all patients to exclude vesicular mole and multiple pregnancies. It was also done for assessment of the gestational age using crown-rump length. No statistically significant difference was found in haemoglobin or haematocrit values. Blood urea was significantly higher in the group of HG treated conventionally both before and after treatment. Serum creatinine did not show any statistically significant difference in both groups of HG patients. The same could be said about serum electrolytes. Before treatment no statistically significant difference was found in serum uric acid levels of both groups of HG patients. Serum total bilirubin, ALT and AST were comparable in both groups. Although the mean serum estradiol level of both groups of HG patients was significantly higher than that of control subjects, yet before treatment, the mean value of serum estradiol in HG patients treated with micronized progesterone was found not to be significantly different from that of HG patients treated conventionally. Before treatment, the mean serum progesterone value of HG patients treated with micronized progesterone was found to be not significantly different from that of HG patients treated conventionally or that of control subjects. Before treatment, HG patients treated conventionally had a significantly higher E2/P ratio than normal controls. In HG patients treated with micronized progesterone, the E2/P ratio before treatment did not differ significantly from that of group II patients or normal control subjects. The E2/P ratio after treatment was significantly lower in HG patients treated with micronized progesterone when compared to those HG patients who were treated conventionally, but it was still significantly higher than that of control subjects. Estradiol is implicated in NVP. Serum levels of estradiol are significantly higher in hyperemetic patients compared to normal pregnant women. When balance is restored by increasing natural progesterone levels, these symptoms typically disappear. Therefore, micronized progesterone has a significant beneficial effect to treat Egyptian pregnant women suffering from hyperemesis gravidarum