Human Reproduction vol 11 no 10 pp 2138-2141, 1996
Does the use of contraception reduce the risk of
pregnancy-induced hypertension?
Eduard Gratac6s1'3, Pere-Joan Torres1,
Vicenc Cararach 1 , Lloren9 Quinto2, Pedro L.AJonso2
and Albert Fortuny1
'Departament d'Obstetricia I Ginecologia and 2Urutat
d'Epidemiologia l Bioestadistica, Hospital CIMc i Provincial,
Universitat de Barcelona, Catalunya, Spain
^To whom correspondence should be addressed at: Departament
d'Obstetricia i Ginecologia, Hospital Clfruc I Provincial, Universitat
de Barcelona, Villarroel 170, 08036 Barcelona, Spain
To estimate the impact of the exposure to spermatozoa on
the risk of developing pregnancy-induced hypertension, the
duration of sexual cohabitation with the father and the
use of contraceptive methods were evaluated among 113
primigravid women with pregnancy-induced hypertension
and 109 age- and parity-matched controls. The duration
of unprotected sexual cohabitation was -50% shorter hi
women with pregnancy-induced hypertension (23 versus
4.7, P <0.0001), regardless of the contraceptive method
previously used. However, the duration of oral contraception use was similar in cases and controls (22.1 versus 23.4
months). Also, of the total group of women who developed
pregnancy-induced hypertension, 85.8% (97) became pregnant during the first 3 months of unprotected sexual
intercourse in comparison with 54.1% (59) in the control
group (P <0.0001). Results suggest that the risk of
pregnancy-induced hypertension in primigravidae is
reduced with duration of sexual cohabitation, and therefore
with exposure to paternal spermatozoa. However, the
protective effect of exposure is not achieved while using
oral contraceptives. Considering the present options for
nulliparous women, contraception does not appear to be a
viable public health policy to reduce the risk of pregnancyinduced hypertension.
Key words: contraception/epidemiology/pre-eclampsia/pregnancy-induced hypertension/sexual cohabitation
Introduction
Pregnancy-induced hypertension has long been considered to
have an immunological basis, as its frequency is largely
increased with primigravidae and rarely affects multigravid
women unless there is a change in paternity (RobiJlard et ai,
1993). This concept has been supported by the results of
several studies suggesting that repeated exposure to father's
spermatozoa prior to conception may reduce the risk of
pregnancy-induced hypertension in the first pregnancy (Marti
and Hermann, 1977). A recent prospective study in 1011
2138
pregnant women reported a strong inverse association between
the length of sexual cohabitation with the father and the risk
of pregnancy-induced hypertension, suggesting that extended
duration of sexual intercourse might reduce this nsk (Robillard
et al., 1994).
If extended duration of cohabitation with the father protects
against pregnancy-induced hypertension, it could be assumed
that this may be related to the contact of spermatozoa with
the female genital tract. However, it remains to be established
whether the risk of developing pregnancy-induced hypertension
is dependent on the type of contraception used. This could
have important implications in the prevention of pregnancyinduced hypertension, as different contraceptive methods allow
contact at different levels of the genital tract. In this study, we
have evaluated the duration of exposure and the impact of
different contraceptive methods, and therefore the influence of
exposure to spermatozoa while using contraception, on the
risk of developing pregnancy-induced hypertension.
Materials and methods
The study was carried out on women delivering at the Hospital Clinic,
Universitat de Barcelona, Spain, from January 1988 to December
1994. Cases were defined as primigravid women with a diagnosis of
pregnancy-induced hypertension Women with previous miscarriages
or terminations were not considered for the study. A total of 178
cases were identified, 90 with pre-eclampsia and 88 with gestational
hypertension. The definitions used for pre-eclampsia and gestational
hypertension were those of the World Health Organization and the
International Society for the Study of Hypertension in Pregnancy
(Zuspan, 1987). Briefly, gestational hypertension was diagnosed if a
previously nonnotensive woman had two repeated (4 h apart) blood
pressure measurements s=90 mm Hg after 20 weeks gestation. Preeclampsia was diagnosed if proteinuna of >300 mg/1 in 24 h was
also present in a woman with gestationa] hypertension.
Among the 178 cases, 42 (23.5%) women were not included
because one or more of the following criteria were present' preexisting disease, e.g. renal or endocrine, (6.1%), obesity, i.e. body
mass mdex 2*30 (12.3%), multiple pregnancies (4.4%), history of
infertility (4.4%), incorrect or mcomplete data in the chart (6.7%).
This left 136 women, 70 with pre-eclampsia and 66 with gestational
hypertension. For each case, the next primigravid woman who
delivered a full-term healthy baby without any of the exclusion
criteria of the study, was used as a control.
Through a telephone interview, following oral informed consent,
and using a structured questionnaire, women were asked about
duration of sexual cohabitation with the father before the first
pregnancy, type and duration of contracepuve methods used, and
duration of sexual intercourse without contraception before pregnancy.
All women were interviewed by the same person, who was not aware
of the hypothesis of the study, and did not know the diagnosis in
each case.
© European Society for Human Reproducuon and Embryology
Contraception and risk of pregnancy hypertension
Table I. Characteristics of study and control populations
Number of women
Mean age at delivery, years (SD)
Contraception used (%)
None
Exclusively barrier methods
Oral contraceptives
Controls
Pregnancy-induced
hypertension
118
25 5 (4 6)
120
25 8 (4 7)
21
18
60
23
16
61
Table IIL Durauon of sexual cohabitauon and of use of contraception,
expressed in months (SD), for hypertensive and healthy pregnant women, in
the group of women with no exposure to father's spermatozoa (DO previous
sexual cohabitation or exclusive use of condoms) before attempting
pregnancy
Duration of cohabitauon with condoms (months)
Duration of unprotected cohabitauon (months)
Controls
(n = 43)
Cases
(n = 45)
13 1 (22 5)
4 7 (3 9)
10 6 (18 4)
2 8 (2 5)*
*Mann-Whitney U test. P = 0009
Table EL Total duration of sexual cohabitation and of use of different
contraceptive methods, expressed in months (SD), among women with
pregnancy-induced hypertension and matched controls
Total duration of sexual cohabitation
Duration of cohabitation with oral
contraceptives
Duration of cohabitation with condoms
Duration of unprotected cohabitation
Controls
(n = 109)
Cases
(n = 113)
42 7 (37 8)
22 1 (32 2)
38.9 (33 7)
23.4 (28 5)
15 9 (214)
4 7 (4 4)
13 1 (18 2)
2 3 (2 3)*
*Mann-Whitney U test P <0 0001
Women reported either no previous cohabitation before attempting
pregnancy, withdrawal, barrier methods (condoms exclusively), and
oral contraceptives. No cases or controls reported the use of an mtrautenne device (IUD). The few women reporting the use of withdrawal
as a contraceptive method were excluded from analysis With this
method, the degree of exposure to spermatozoa may be variable, and
this could result in a classificanon bias. Therefore, the women in the
study were separated into two groups on the basis of the type of
exposure to the father's spermatozoa before attempting pregnancy
(l) no previous exposure to spermatozoa, i e no previous sexual
intercourse with the father, or having used condoms exclusively
before attempting pregnancy; (n) previous exposure to spermatozoa,
l e. women using oral contraception, exclusively or alternaUng with
other methods.
We compared the following periods of tune (in months), (I) total
duration of sexual cohabitauon with the father before the first
pregnancy, regardless of the use and methods for contraception,
(n) duration of intercourse with barrier methods, (ni) duration of
exposure to spermatozoa with the use of oral contracepUon; and
(iv) durauon of exposure while attempting pregnancy, i.e the period
of unprotected sexual intercourse before conception.
Statistical analysis
Data were analysed with the statistical package SPSS for Windows
The Mann-Whitney U and %2 tests were used to evaluate the possible
differences in the groups studied
Results
Of 272 women, 120 (88.2%) cases and 118 (86.7%) controls
were interviewed; 11.7% of cases and 12.5% of controls were
not found. All cases agreed to answer the questionnaire, but
one control refused. Seven cases and nine controls reported
the use of withdrawal, which left a total of 113 cases and
109 controls. Groups were similar in age, ethnic group,
contraceptive methods used, and date of delivery (Table I).
Results on the durauon of exposure in women with preg-
Table IV. Durauon of sexual cohabitauon and of use of different
contraceptive methods, expressed in months (SD), for hypertensive and
healthy pregnant women, m the group of women with exposure to father's
spermatozoa (oral contracepuves users) before attempung pregnancy
Durauon of cohabitauon with oral
contracepuves (months)
Durauon of cohabitauon with condoms
(months)
Durauon of unprotected cohabitation
(months)
Controls
(n = 66)
Cases
(/i = 68)
36 4 (34 5)
38 9 (27 2)
17 7 (20 6)
14 8 (18 4)
4 7 (4 6)
2 1 (2 1)*
•Mann-Whitney U test P <0.0001
nancy-induced hypertension and healthy pregnant women are
presented in Table II. Among all women studied, the total
duration of sexual cohabitation in those with pregnancyinduced hypertension was shorter by an average of 5 months.
However, this difference did not reach statistical significance.
Duration of use of oral contraceptives was practically identical
among cases and controls. The duration of use of barrier
methods was slightly lower in women who developed pregnancy-induced hypertension, but, again, the difference does
not reach statistical significance. However, the mean duration
of unprotected sexual cohabitation, i.e. duration of exposure
while attempting pregnancy, was ~50% lower in hypertensive
women in comparison with healthy women, regardless of
the previous use of contraceptive methods. Further analysis
compared the same periods of sexual cohabitation and type of
contraception in the groups of women (i) with no exposure
to spermatozoa (no sexual cohabitation or using condoms
exclusively) pnor to attempting pregnancy, and (ii) those who
had used oral contraceptives.
In women having no previous exposure to spermatozoa
(Table HI), the duration of unprotected sexual intercourse, and
therefore of exposure, was significantly reduced in those who
had developed pregnancy hypertension in comparison with
controls (2.8 versus 4.7 months, P <0.01), but the total
duration of sexual cohabitation and the duration of the use of
barrier methods showed no significant differences between
cases and controls.
In women who had used oral contraceptives (Table IV), the
length of time of unprotected sexual intercourse was again
significantly shorter in hypertensive women than in healthy
pregnant women (2 1 versus 4.7 months, P <0.001). However,
the mean duration of oral contraceptive use was similar in
2139
E.Grata«Ss et aL
both groups (36.4 versus 38.9 months). Duration of the use of
barrier methods was slightly reduced m women with pregnancy-induced hypertension, but the difference was not
statistically significant.
Finally, of all women who developed pregnancy-induced
hypertension, 55 (48.6%) became pregnant during the first
month of unprotected sexual intercourse in comparison with
28 (25.6%) in the control group (P <0.001). In the first
3 months of unprotected sexual cohabitation, 85.8% (97)
hypertensive women became pregnant [in comparison with
54.1% (59) controls; P <0.0001]. Within the group of cases,
79.6% (43/54) of women with gestational hypertension and
91.5% (54/59) of women with pre-eclampsia became pregnant
during the first 3 months of unprotected sexual intercourse
(P <0.01 and P <0.0001 when compared with controls
respectively).
Discussion
Our data support the results of previous studies suggesting a
decrease in the risk of pregnancy-induced hypertension as the
time of previous sexual cohabitation with the father increases.
However, this study attempts to further address whether there
are any implications of the use of contraceptive methods
in the prevention of pregnancy-induced hypertension. The
population under study has a relatively high prevalence of oral
contraceptive use in nulliparous women, and this allowed us
to evaluate the duration of exposure to paternal spermatozoa
with and without the use of this method. Our findings strongly
suggest that exposure to paternal spermatozoa exclusively
while using oral contraception is not a protective factor against
the risk of developing pregnancy-induced hypertension in
primigravidae. On the contrary, the length of unprotected
sexual cohabitation before pregnancy showed a significant
inverse association with the nsk of pregnancy-induced hypertension, regardless of the type of contraceptive method previously used. The data suggest that the use of oral
contraceptives induces some modifications that block the
immunological protective response that occurs during unprotected cohabitation.
Oral contraceptives act at different levels of the female
reproductive tract, i.e. cervical mucus thickening, tubal motility,
endometrial lining, and ovulation suppression. However, in
terms of exposure to spermatozoa, the main difference in a
woman taking contraceptives is that the characteristics of
cervical mucus may confine the semen to the vagina. Oral
contraceptives induce changes in cervical mucus properties
that make it impenetrable to spermatozoa (Wolf et al., 1979),
thus confining the spermatozoa to the vagina. If this was the
mechanism for the non-protective effect of oral contraceptives,
it would have important implications. Firstly, intrauterine or
higher level exposure might be necessary to protect against
pregnancy-induced hypertension, and contraception using
methods which allow only vaginal exposure to spermatozoa
would not be a viable option for the prevention of the condition.
Secondly, this suggests that contact with spermatozoa might
not result in the same immune response at different levels of
the genital tract. It remains to be established whether the use
2140
of methods allowing for an intrauterine contact with sperm,
such as IUD, could influence the risk of pregnancy-induced
hypertension. An alternative explanation for our findings is a
possible effect of oral contraception on histological and/or
functional characteristics of the reproductive tract, resulting
in modification of the natural immunological interaction of
spermatozoa with the mucosae, thus limiting the response to
paternal sperm antibodies.
The observed differences between normal and hypertensive
women in terms of unprotected sexual intercourse were slightly
more marked in women with pre-eclampsia than in women
with gestational hypertension. Gestational hypertension is
a more heterogeneous disease than pre-eclampsia, with an
important proportion of cases representing latent essential
hypertension (Chesley, 1989) and therefore implying a less
specific case definition. We excluded many cases from the
study attempting to evaluate only those women in whom
hypertension was most likely induced by pregnancy. However,
the probability of including women with undiagnosed predisposing conditions or latent chronic hypertension was probably
higher in women with gestational hypertension than in women
with pre-eclampsia.
This is a retrospective study and an insurmountable weakness
is the possibility that some women reported inaccurate data
on the duration of sexual intercourse. However, the probability
of reporting erroneous data was the same for cases and controls.
The interviewer did not know the diagnosis in each case, all
women were interviewed using the same structured questionnaire, and both study groups were similar in age, ethnic
group, contraceptive methods used, and date of delivery. The
possibility that inaccuracy influenced the differences found
between cases and controls appears to be small. Furthermore,
results are consistent, as the recorded duration of use of oral
contraceptives or condoms is similar for women with and
without hypertension. Therefore, although one should always
be cautious in interpreting results from a retrospective evaluation, we believe the differences found in the duration of
unprotected sexual cohabitation are strong enough to encourage
further prospective research evaluating the hypothesis of the
study.
In summary, this study supports previous evidence that the
risk of pregnancy-induced hypertension in primigravid women
is reduced with increasing duration of sexual cohabitation and
exposure to the father's spermatozoa (Robillard et al., 1994).
However, the data suggest that the protective effect is not
achieved with exposure during the use of oral contraception.
Further research is required to evaluate whether protection
against pregnancy-induced hypertension depends on intrauterine exposure to spermatozoa, and therefore whether
immunological response to paternal antigens occurs only at
certain anatomical levels of the reproductive tract. Barrier
methods or oral contraceptives do not seem to modify the risk
of pregnancy-induced hypertension, and methods such as IUD,
that allow for intrauterine exposure, are of limited use in
nulliparous women (Grimes, 1989). Therefore, at present, the
use of contraception to reduce the risk of pregnancy-induced
hypertension does not appear to be a viable public health option.
Contraception and risk of pregnancy hypertension
References
Chesley, L C (1989) Mild preeclampsia. potentially lethal for women and for
advancement of knowledge. Clm. Exp Hypertens., B8, 3-12
Gnmes, D.A (1989) Whither the intrauterine device7 Clm. Obstet Gynecol,
32, 369-381
Mart), JJ. and Hermann, U (1977) Immunogestosis. a new etiologic concept
of 'essential' EPH gestosis, with special consideration of the prurugravid
patient Am. J. Obstet. Gynecol, 128, 489-493
Robillard, PL, Hulsey, T C , Alexander, G.R. et al (1993) Paternity patterns
and risk of preeclampsia in the last pregnancy in multiparae J Rcprod.
Immunol, 24, 1-12
Robillard, P I., Hulsey, T.C , Penarun, J el aL (1994) Association of pregnancyinduced hypertension with duration of sexual cohabitation before conception
Lancet, 344, 973-975.
Wolf, D O , Blasco, L , Khan, M A. and Litt, M (1979) Human cervical
mucus V Oral contraceptives and mucus rheologic properties Fend.
StenL, 32, 166-169
Zuspan, F.P (1987) The Hypertensive Disorders of Pregnancy Report of
a WHO Study Group. Technical Report Series no 758 World Health
Organization, Geneva.
Received on March 4, 1996, accepted on August 9, 1996
2141