European Journal of Cardiovascular Medicine

Pregnancy induced hypertension may occur in about 3-10% of all pregnancies [1,2]. It remains a most important cause of perinatal and maternal morbidity and mortality worldwide, because of complications such as preeclampsia, eclampsia, fetal growth retardation, premature birth or abruptio placentae [3]. Total testosterone (TT) levels in the female are normally found to be much lower than those encountered in the healthy male. Adrenal glands and the ovaries, secreted testosterone in small quantity and in healthy women 50–60% of the daily testosterone production arises from peripheral metabolism of pre-hormones, chiefly androstenedione [4].

Hypertension is a highly predominant condition and accountable for half of the cardiovascular mortality and morbidity, causing a massive burden on the world population [5].High blood pressure (BP) affects multiple organs and is the principal modifiable risk factor for cardiovascular disease (CVD), such as myocardial infarction, coronary heart disease, and stroke [6].

According to literature, several researchers showed that elevated serum TT level can be a diagnostic marker of preeclampsia. These considerable evidence suggests

relationship between serum TT and preeclampsia [7-10]. We therefore studied whether the serum TT concentration dose correlate with mean arterial blood pressure (ABP) and might indicate the severity of preeclampsia.

This study was carried out at Department of Biochemistry, Grant Government Medical College and Sir J.J. Group of Government Hospitals, Mumbai.All study subjects completed a clinical history form and gave informed consent.

Inclusion criteria

Fifty preeclamptic patients in the age group of 18 to 35 years were studied for estimation of serum TT. Patients with symptoms and signs suggestive of preeclampsia supported by laboratory investigations were included in the study.

Exclusion criteria

Study subjects with hypertension, proteinuria, and edema. None of the subjects had history of polycystic ovary syndrome, Liver diseases, renal diseases, human immune deficiency virus infection.

Withdrawal Criteria

Specimen collected in inappropriate container. Lipemic or hemolyzed sample. Missing of adequate information. Insufficient quantity of sample will be withdrawn from the study.

Control group

Age matched 50 healthy normotensive pregnant subjects of identical age without any disease were enrolled, who attended to the Gynecology OPD.

Ethical aspect

The study approved by Institutional Ethical Committee,Grant Medical College and Sir J.J. Group of Government Hospitals, Mumbai, India,(vide letter- IEC/Pharma/456/07).

Sample collection and analysis

Venous blood samples were collected in red color-coded vacutainer with aseptic precautions. Blood sample was centrifuged at 3000 rpm for 5 minutes after 2 hours of the collection. Serum was separated and collected in 5 ml micro tube with cork. The serum sample with no hemolysis used for the quantitative estimation of serum TT on fully automated enzyme amplified chemiluminescent immunoassay based Immulite 1000 analyzer.Solid-phase, competitive, chemiluminescent enzyme immunoassay method was used for the measurement of serum TT [11]. Measurement of serum TT by using commercial kits from Siemens Medical Solutions Diagnostics, Los Angeles, CA, USA.

Measurement of blood pressure

The standard sphygmomanometer technique was used to measure blood pressure. Patients were allowed to rest for 30 minutes. All measurement taken with the help of Clinician. Hypertension was defined as a systolic blood pressure reading greater than 140 mm of Hg and/or a diastolic blood pressure reading greater than 90 mm of Hg. Numerical variables were reported in terms of mean and standard deviation.

Statistical analysis

All the collected study data was entered into an MS-Excel sheet and analyzed by using normal distribution ‘Z’ test. In this analysis, variables showing p value less than 0.05 and 0.001 were considered to be statistically significant and highly significant respectively. Correlation coefficient (r) was calculated for finding correlation between two biochemical parameters by using simple linear regression analysis.

The clinical characteristics of the enrolled pregnant women were not given in the tabular form. The preeclampsia group (n = 50) and the normotensive pregnant group (n = 50) had similar maternal age, parity, gravidity, and hemoglobin levels. However, the preeclampsia group had higher blood pressure, maternal body mass index, nulliparity proportion and markedly decreased infant birth weight and gestational age. There was a significant difference ingestational age at delivery, body mass index, systolic blood pressure, diastolic blood pressure, fetal weight, and fetal length between preeclampsia and normotensive control groups.

Table 1: Serum TTand MBP levels in controls and preeclamptic patients.

Preeclampsia patients exhibited different levels of circulating serum TT and MBP.Their mean ± SD age and gestational age at time of study was 23.6 ± 4.16 years and 32.4 ± 6.05 weeks respectively. Table 1 depicts changes in serum TT and mean arterial blood pressure (MBP) levels when control group was compared with study group of preeclampsia. As can be seen, significant increase, (p< 0.001) was observed in both serum TT and MBP level in patients with preeclampsia.

Table 2: Correlation of serum TTand MBP in preeclamptic patients.

We further calculated; correlation coefficient (r) between serum TT and MBPby using simple linear regression analysis. We found, positive and highly significant (r = 0.528, P < 0.001) correlation was observed between serum TT compared with MBP in preeclampsia. (Table 2). 

Hypertension is measured to be the most vital risk factor of cardiovascular disease, which justifies extensive attention worldwide [12].However, it has a high underdiagnosis rate and low consciousness among pregnant women in rural areas with poor education background.

In this study, we found that levels of serum TT were altered in preeclampsia patients than in age-matched normotensive pregnant controls. In preeclampsia patients MBP showed significant different as compared with those of controls. Importance of MBP as clinical parameter has been recognized estimating cardiovascular disease risk factor due to their positive association with hypertension [13].

Lan KC et al compared patients with preeclampsia and patients with uncomplicated pregnancies in terms of serum steroid hormones. They found subjects with preeclampsia had lower levels of steroid hormones, estrogen, and estrogen receptor-α, but higher levels of T and estrogen receptor-β. They suggested that, these molecules may have roles in the pathogenesis of preeclampsia [14].

Ibrahim ZM et al evaluated, the association between fetal gender, serum beta-human chorionic gonadotropin (HCG), and serum testosterone in preeclampsia. They found positive association between the male gender of the fetus and preeclampsia. Increased HCG and testosterone were associated with developing preeclampsia [15].

Testosterone plays a crucial role in regulating blood pressure by activating both vasoconstriction and vasorelaxation, while free testosterone is a derived measure as the metabolically active segment with certain limitations[16].Sex hormone– binding globulin, the major circulating protein that binds to and carriages steroid sex hormones, also has cardiometabolic effects [17].

KeyaSL et al. studied relationship between Free Testosterone and Preeclampsia. They found a significant positive correlation between systolic and diastolic blood pressure with free testosterone. Also, they showed levels of the free testosterone were significantly higher in women with preeclampsia than in normotensive women. thus concluded, testosterone might have role in the pathogenesis of preeclampsia [18].

In many studies revealed that there are no changes in the levels of androgens especially testosterone in preeclampsia and these hormones do not play clinically significant role in the pathogenesis of the disease [19,20].However most studies showed increase of androgen especially testosterone levels were cited as the cause of preeclampsia pathogenesis [7-10]. Our findings about serum TT levels are compatible with results of these studies.

Positive and highly significant correlation (r = 0.528, P < 0.001) was observed between serum TT compared with MBP in preeclampsia. Their 95% confidence interval of correlation coefficient ‘r’ was ranged from 0.293 to 0.703 (figure 1). Most of the studies on human and animal showed the relationship between androgens, especially testosterone and hypertension [21-25].This study also supports our findings in Indian women.

The concentrations of the potent total testosterone were significantly higher in women with preeclampsia than in normotensive women with similar gestational and maternal ages. This change may indicate a role of the testosterone in the pathogenesis of preeclampsia. The present study found a significant association between serum TT and mean blood pressure as a risk factor for cardiovascular disease (CVD) and trophoblastic dysfunction in preeclampsia.

Limitations of the study

This is short term project have been limited to a comparatively small number of cases of preeclampsia. However, limitation of our study is small sample size, so more studies with good sample size are required to corroborate these results.

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