MATERNAL SERUM DEHYDROEPIANDROSTERONE SULFATE LEVELS AND SUCCESSFUL LABOR INDUCTION

Abstract

To evaluate the maternal serum dehydroepiandrosterone sulfate level as a factor associated with the outcome of labor induction. Venous blood was collected from 45 women at the initiation of labor induction. Pregnancies complicated by maternal corticosteroid use, antepartum chorioamnionitis, or cesarean delivery for indications other than arrest disorders, were excluded from analysis. In 42 women meeting inclusion criteria, induction followed established protocol. Serum dehydroepiandrosterone sulfate levels were measured by radioimmunoassay and correlated with the outcome of each induction attempt. A successful result was defined as progression to active labor. The welch approximate t-test, Mann-Whitney test, Fisher exact test, simple regression, and multiple regression were used for statistical analysis, with p<0.05 considered to be significant. The mean (±standard error) dehydroepiandrosterone sulfate level was higher in women who progressed to active labor (n=25) than in those with unsuccessful attempts (n=17), (48.63±6.53 µg/dl versus 26.86 ± 5.17 mg/dl, respectively; p= 0.03). Compared with women with dehydroepiandrosterone sulfate levels above 60 µg/dl, women with lower levels had an unsuccessful induction odds ratio (OR) of 6.92 (95% confidence interval 1.74, 32.52, p= 0.01). The OR increased as dehydroepiandrosterone sulfate levels decreased. Dehydroepiandrosterone sulfate may be an important factor in successful labor induction. Acta Medica Iranica, 41(2): 91-93; 2003

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MATERNAL SERUM DEHYDROEPIANDROSTERONE
SULFATE LEVELS AND SUCCESSFUL LABOR INDUCTION
M. Modarres-Gilani and N. paykari
Department of Gynecology and obstetrics, Vali-e-asr Hospital, Faculty of Medicine, University of Medical Sciences,
Tehran, Iran
Abstract- To evaluate the maternal serum dehydroepiandrosterone sulfate level as a factor associated with the outcome of
labor induction. Venous blood was collected from 45 women at the initiation of labor induction. Pregnancies complicated by
maternal corticosteroid use, antepartum chorioamnionitis, or cesarean delivery for indications other than arrest disorders, were
excluded from analysis. In 42 women meeting inclusion criteria, induction followed established protocol. Serum
dehydroepiandrosterone sulfate levels were measured by radioimmunoassay and correlated with the outcome of each induction
attempt. A successful result was defined as progression to active labor. The welch approximate t-test, Mann-Whitney test,
Fisher exact test, simple regression, and multiple regression were used for statistical analysis, with p<0.05 considered to be
significant. The mean (±standard error) dehydroepiandrosterone sulfate level was higher in women who progressed to active
labor (n=25) than in those with unsuccessful attempts (n=17), (48.63±6.53 µg/dl versus 26.86 ± 5.17 mg/dl, respectively; p=
0.03). Compared with women with dehydroepiandrosterone sulfate levels above 60 µg/dl, women with lower levels had an
unsuccessful induction odds ratio (OR) of 6.92 (95% confidence interval 1.74, 32.52, p= 0.01). The OR increased as
dehydroepiandrosterone sulfate levels decreased. Dehydroepiandrosterone sulfate may be an important factor in successful
labor induction.
Acta Medica Iranica, 41(2): 91-93; 2003
Key Words: Maternal serum dehydroepiandrosterone sulfate, labor induction
INTRUDUCTION
Dehydroepiandrosterone (DHEA) sulfate is a weak
androgenic steroid produced by the adrenal cortices of
the pregnant woman and her fetus.
Binding sites for DHEA sulfate have been
identified on the plasma membranes of human cervical
fibroblasts (1), suggesting that the hormone may play a
role in cervical connective tissue function.
Although DHEA sulfate administration has been
reported to induce cervical ripening (2), and labor
(3,4), the influence of endogenous maternal serum
DHEA sulfate levels on the outcome of an induction
attempt has not been defined. Among young nulliparas
in labor at term, this level has been found to be
significantly lower in women requiring oxytocin
augmentation of labor than in those progressing
spontaneously (5). We hypothesized that the
endogenous maternal serum DHEA sulfate level is a
factor that affects the outcome of labor induction.
Received: 17 July 2001, accepted: 12 March 2003
Corresponding Author:
Department of Gynecology and obstetrics, Vali-e-asr Hospital, Faculty
of Medicine, University of Medical Sciences, Tehran, Iran
Tel: +98 21 6930666
Fax: +98 21 6937766
More specifically, women with higher DHEA
sulfate levels would be more likely to have successful
labor inductions.
MATERIALS AND METHODS
Fourty five women with singleton pregnancies
undergoing labor induction were recruited
prospectively over the course of 4 months. Use of
corticosteroids, including those administered
antenatally for fetal lung maturation, and antepartum
chorioamnionitis, were criteria for exclusion due to
their respective associations with potential adrenal
suppression and myometrial dysfunction. All women
had Bishop scores less than 5.
After obtaining informed consent and before
initiation of induction, blood samples were collected
and serum was stored at –20°C until analyzed.
Cesarean delivery for nonreassuring intrapartum fetal
testing, vaginal bleeding, malpresentation, or fetal
weight over 4000g further excluded 3 patients from
analysis. For the 42 women fulfilling criteria,
induction of labor was attempted following established
protocols with intravenous oxytocin.

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Maternal serum DHEA and labor induction
92
Dehydroepiandrosterone sulfate levels were
measured by radioimmunoassay with commerical kits
obtained from Kavoshyar co.
Each sample was assayed twice, with the reported
dehydroepiandrosterone sulfate level was the average
of the two determinations. Serum dehydroepi-
androsterone sulfate levels were then correlated with
the success or failure of an induction attempt. Using
the definition of Watson et al (6), an induction attempt
was termed “successful” if the patient reached the
active phase of labor as demonstrated by a change in
the slope of cervical dilation. Twenty five of the
induction attempts were successful.
The preinduction dehydroepiandrosterone sulfate level
and age of those women with successful induction
attempts were compared with those with unsuccessful
attempts using the Welch approximate t- test. Similar
analysis were used for statistical comparison of birth
weight, gestational age and parity. Bishop scores in the
two groups were compared using the nonparametric
Mann-Whitney test. P<0.05 was considered
statistically significant.
RESULTS
Compared the women with successful induction
attempt the women with unsuccessful attempts had
significantly lower preinduction Bishop scores
(2.27±0.27 versus 3.05±0.23; p=0.03) (Table 1).
Table 1. Characteristics of the study population
Successful
Induction
(n=25)
Unsuccessful
Induction
(n=17)
P
Maternal
age(y) 24.73±1.01 24.09±1.07 0.66
Gravidity 1.82±0.26 1.63±0.24 0.73
Gestational
age(d) 288.41±1.08 286.09±1.33 0.14
Birth
weight(g) 3485.29±101.71 3530.90±112.37 0.85
Bishop
scores 3.05±0.23 2.27±0.27 0.03
Parity 0.63±0.19 0.45±0.20 0.57
Dilation 1.5294±0.17 1.1818±0.18 0.11
No other statistically significant demographic
differences were identified between the two groups.
The mean (± standard error) dehydroepiandros-
terone sulfate level was significantly higher in women
with successful induction than in women with
unsuccessful attempts (48.63±6.53 µg/dl versus
26.86±5.17 µg/dl, respectively (P= 0.035). The main
cause of cesarean was failure of labor progress
(77.8%).
Table 2. Relationship between maternal serum dehydroepiandrosterone sulfate levels and the incidence of
unsuccessful induction of labor
DHEA sulfate (µg/dl) Incidence of unsuccessful
induction
Odds ratio 95% confidence interval
≤ 80 40
17 (42%)
> 80 2
0 (0%)
2.95 0.57, 15.27
≤ 70 34
16 (74%)
>70 8
1 (12%)
6.22 0.84, 46.44
≤ 60 28
15 (53%)
>60 14
2 (14%)
6.92 1.47, 32.52
≤ 50 24
14 (58%)
>50 18
3 (16%)
7.00 1.72, 28.41
≤ 40 23
14 (60%)
>40 19
3 (21%)
8.29 2.05, 33.48
≤ 30 20
14 (70%)
>30 22
3 (27%)
14.77 4.05, 59.90

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Acta Medica Iranica, Vol. 41, No. 2 (2003)
93
When dehydroepiandrosterone sulfate levels were
equal to or below 60 µg/dl, the OR for an unsuccessful
induction increased progressively as the maternal
serum dehydroepiandrosterone sulfate level decreased
(Table 2). At levels above 60 µg/dl, the OR for an
unsuccessful induction was not statistically significant.
DISCUSSION
Parenteral adminstration of dehydroepiandros-
terone sulfate has been used effectively for cervical
ripening and labor induction. The proposed mechanism
of action is an activation of total collagenolytic
activity, resulting in uterine connective tissue
remodeling. Recent animal studies (7) have suggested
that dehydroepiandrosterone sulfate acts
synergistically with interleukin-8 to increase
collagenase, elastase, and gelatinase activity while
decreasing the cervical collagen content. The cervical
collagenolytic effect of dehydroepiandrosterone sulfate
may also be mediated through prostaglandin E2
because its synthesis is enhanced by dehydroepi-
androsterone sulfate in human cervical tissue (8).
Sufficient uterine connective tissue remodeling is
important in allowing normal labor progression (9).
Our study provides clinical support for these
animal and culture studies, suggesting a role for
DHEA sulfate in successful induction of labor in
humans. The endogenous preinduction dehydroepi-
androsterone sulfate levels were significantly lower in
patients with unsuccessful inductions than in those
with successful inductions: additionally, the OR for an
unsuccessful attempt increased progressively with
decreasing dehydroepiandrosterone sulfate levels
below a critical level (60 µg/dl). Above that, the OR
did not meet statistical significance, perhaps due to a
true threshold level.
As further evidence for a role of endogenous
DHEA sulfate in successful labor induction, our study
agrees with that of Liapis et al (10) in showing an
association between higher Bishop scores and higher
DHEA sulfate levels. The same investigators (10)
found no such correlation with estradiol, estriol,
progesterone, or cortisol, suggesting a direct role for
DHEA sulfate (and not its metabolites) in uterine
collagenase activation.
The levels of preinduction maternal serum DHEA
sulfate appears to influence the ultimate outcome
(success or failure) of an induction attempt. Although
the mechanism of this action of dehydroepi-
androsterone sulfate remains to be clarified, available
evidence implicates collagenase activation and a
resultant remodeling of uterine connective tissue.
Consequently, dehydroepi-androsterone sulfate may be
an important factor in successful labor induction.
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