Steroid Hormones and Disease Activity DuringPregnancy in Systemic Lupus ErythematosusANDREA DORIA,1 MAURIZIO CUTOLO,2 ANNA GHIRARDELLO,1 SANDRA ZAMPIERI,1

FRANCESCA VESCOVI,1 ALBERTO SULLI,2 MASSIMO GIUSTI,2 ANTONIO PICCOLI,1

PASQUALE GRELLA,1 AND PIER FRANCA GAMBARI1

Objectives. To analyze the variation of steroid hormone levels during pregnancy in patients with systemic lupuserythematosus (SLE). Moreover, to investigate whether, during gestation, there is any relationship between steroidconcentration and SLE activity.Methods. Seventeen consecutive pregnant SLE patients and 8 matched healthy pregnant controls were studied prospec-tively. Disease activity was evaluated by European Consensus Lupus Activity Measure (ECLAM) score modified forpregnancy. The following hormones were evaluated: testosterone, 17�-estradiol (estradiol), cortisol, dehydroepiandros-terone sulfate (DHEAS), and progesterone.Results. Disease activity score significantly varied during pregnancy and postpartum (P < 0.05), being decreased in thethird trimester and increased in the second trimester and postpartum. Serum levels of all steroids varied significantlyduring pregnancy and the postpartum period both in patients and in healthy subjects. In SLE patients, estradiol,progesterone, and DHEAS concentrations were found to be significantly reduced compared with controls. Serum levelprofiles of estradiol and progesterone were different from those observed in controls. No differences in the steroid levelswere observed between patients taking prednisone <5 mg/day or >5 mg/day, apart from cortisol, which was, as expected,lower in the latter group.Conclusions. The major hormonal alteration observed during pregnancy in SLE patients was an unexpected lack ofestrogen serum level increase, and, to a lesser extent, progesterone serum level increase, during the second and—evenmore—the third trimester of gestation. This lack of increase probably was due to placental compromise. Therefore, thesesteroid hormone variations may result in a lower humoral immune response activation, probably related to a change inthe estrogen/androgen balance, that in turn could account for the decrease in disease activity observed during the thirdtrimester in pregnant SLE patients.

KEY WORDS. Systemic lupus erythematosus; Pregnancy; Steroid hormones; SLE activity; Estrogens.

INTRODUCTION

The susceptibility to autoimmune diseases, such as rheu-matoid arthritis (RA) and systemic lupus erythematosus

(SLE), arises from complex interactions between severalgenetic, hormonal, and environmental predisposing fac-tors. Steroid hormones play a relevant role because of theirstrong modulating effects on the immune system (1–9).Steroid hormones account for the higher immune reactiv-ity and susceptibility to autoimmunity in women com-pared with men during the reproductive age. Estrogensseem to be mainly implicated as major enhancers of theimmune response, whereas cortisol and androgens seem toact as natural suppressors (2–4).

In particular, a recent study confirms that 17�-estradiolis able to polyclonally increase the production of IgG,including IgG anti–double-stranded DNA, in SLE patients’peripheral blood mononuclear cells by enhancing B cellactivity and by promoting interleukin-10 (IL-10) produc-tion by monocytes (5).

Pregnancy is a physiologic condition in which the sexhormone balance is modified to achieve immunosuppres-

This work was supported by “Ministero dell’Universitae della Ricerca Scientifica e Tecnologica” project9906242552-003, “Autoanticorpi e danno d’organo nellemalattie autoimmuni sistemiche.”

1Andrea Doria, MD, Anna Ghirardello, PhD, SandraZampieri, PhD, Francesca Vescovi, MD, Antonio Piccoli,MD, Pasquale Grella, MD, Pier Franca Gambari, MD: Uni-versity of Padova, Padua, Italy; 2Maurizio Cutolo, MD, Al-berto Sulli, MD, Massimo Giusti, MD: University of Genova,Genoa, Italy.

Address correspondence to Andrea Doria, MD, Division ofRheumatology, University of Padova, Via Giustiniani 2,Padua, 35128, Italy. E-mail: adoria@unipd.it.

Submitted for publication August 7, 2001; accepted inrevised form August 28, 2001.

Arthritis & Rheumatism (Arthritis Care & Research)Vol. 47, No. 2, April 15, 2002, pp 202–209DOI 10.1002/art1.10248© 2002, American College of Rheumatology

ORIGINAL ARTICLE

202

sion and tolerance of the immune system to paternal andfetal antigens (10,11). It is well known that estrogens pro-gressively increase in the maternal circulation duringpregnancy, particularly in the third trimester (12). Al-though less markedly, an increase in cortisol, dehydroepi-androsterone sulfate (DHEAS), progesterone, and testoster-one are also observed during pregnancy.

Estrogen immunomodulation is dose dependent (6). Atphysiologic concentrations, estrogens seem to stimulateboth humoral and cellular immune responses (Th2- andTh1-type cytokines). However, at supraphysiologic con-centrations, as achieved during late pregnancy (at least10-fold), estrogens seem to be immunosuppressive, at leaston cell-mediated immune responses (Th1-type cytokines);but they induce antibody production (Th2-type cytokines).Even progesterone and glucocorticoids seem to suppressTh1 (10,13–15) and increase Th2 cytokine production(14–17). The Th2 cytokine polarization could explain whyRA patients generally improve (18) and SLE patientsworsen during pregnancy (19). In fact, in SLE, pregnancyhas long been considered a high-risk event, both for themother and the fetus, because disease flares are frequentlyobserved during gestation, and fetal wastage, prematurity,and low birth weight babies are more common in womenwith SLE than in the healthy population (20–24). In thelast decades, however, it has become apparent that preg-

nancies resulted in favorable outcomes in the majority ofcases, although SLE flares still remain common duringpregnancy and postpartum (22,25–32). Various recent ob-servations suggest that the percentage of SLE flares falls inthe third trimester of pregnancy (22,27,28,31–34), al-though this is the period in which the highest serum levelsof estrogen, progesterone, cortisol, and testosterone shouldbe expected.

There are few studies regarding the relationships amongsteroid hormones, disease activity, and immunologic pa-rameters during pregnancy in SLE (24). To clarify thisimportant and poorly investigated issue, we prospectivelyanalyzed the steroid hormone concentrations, includingestrogen, progesterone, testosterone, DHEAS, and cortisol,in patients with SLE and matched healthy women before,during, and after pregnancy. Moreover, we investigatedwhether there was any relationship among steroid levels,disease activity, and some immunologic parameters.

PATIENTS AND METHODS

Seventeen consecutive successful pregnancies in 17 pa-tients with SLE were prospectively studied. All patients(mean age 30.5 years, range 21–38; mean disease duration91 months, range 18–184) fulfilled the American College

Table 1. Clinical and laboratory findings of SLE patients at conception*

Patientnumber

Diseaseduration(months)

Plannedpregnancy Clinical manifestations Laboratory abnormalities

Autoantibodies(dilution)

ECLAMscore

1 67 yes None 1� Glob ANA (1:160), SSA 02 61 yes Discoid rash, arthralgia Leuko-lymphopenia,

1� glob, 2C3, 2C4ANA (1:2,560), SSA,

dsDNA (1:20), aCL IgM3

3 46 yes None Anemia, 1ESR ANA (1:40), aCL IgG 24 43 no Arthralgia, fatigue,

alopecia, discoidrash, oral ulcers

Leuko-lymphopenia, 2C4 ANA (1:1,280) 3

5 44 no Polyarthritis 1� Glob, 2C3, 2C4 ANA (1:2,560). Sm, SSA 26 178 yes Hypertension Anemia, 1ESR, 2C3, 2C4 ANA (1:1,280) 37 105 yes None Anemia, leuko-lymphopenia,

piastrinopenia, 2C3, 2C4ANA (1:1,280) 2

8 18 no Fatigue, pleuropericarditis,arthralgia

Anemia, lymphopenia,2C3, 2C4, 1RF,

ANA (1:1,280),dsDNA (1:320), SSA

5

9 184 yes Raynaud’s arthralgia,hypertension

1� Glob, 2C4 ANA (1:1,280), nRNP,aCL IgG

0

10 134 yes None Lymphopenia, 2C3 ANA (1:320), dsDNA (1:20),aCL IgG, LA

2

11 35 no None 2C3, 2C4 ANA (1:320) 112 101 no None 2C3 ANA (1:320), dsDNA

(1.160), aCL IgG1

13 30 yes Mild cutaneus vasculitis Anemia, lymphopenia, 2C3 ANA (1:640), SSA, aCL IgG 214 99 yes None Anemia, leuko-lymphopenia,

1� glob, 1RF, 1ESRANA (1:1,280), SSA 2

15 178 yes None Lymphopenia, 1ESR ANA (1:5,120), aCL IgG, LA 216 153 yes None 1� Glob, 2C3, 2C4,

proteinuria �0, 5 g/dayANA (1:5,120) 1

17 86 yes None Anemia, 1ESR, 1� glob ANA (1:10,240) 2

* SLE � systemic lupus erythematosus; C3 and C4 � serum complement fractions; ANA �antinuclear antibodies; SSA � anti-SSA antibody; nRNP� anti-nuclear RNP antibody; Sm �anti-Sm antibody; aCL � anticardiolipin antibodies; LA � lupus anticoagulant; ESR � erythrocyte sedimentationrate; RF � rheumatoid factor; � glob � gamma globulin; dsDNA � anti–double-stranded DNA.

Hormones in Lupus Pregnancy 203

of Rheumatology criteria for SLE (35). Eight pregnancies in8 healthy volunteers (mean age 29 years, range 20–35)were considered as controls. Gestational period was simi-lar in SLE patients (mean 37 weeks, range 31–41) andcontrols (mean 38 weeks, range 35–41).

All patients were enrolled in our protocol for pregnancyplanning and followup and they were evaluated monthlyby the same rheumatologist and obstetrician during theirentire pregnancy, including 10–12 weeks of the postpar-tum period.

Twelve of 17 pregnancies were fully planned and 5pregnancies started unexpectedly. In our protocol, thepregnancy was planned when disease was inactive for atleast 6 months.

At each clinical evaluation, routine laboratory tests wereperformed, including white blood cell count; urinalysis;and glucose, blood urea nitrogen, serum creatinine, IgG,IgM, and IgA levels. Antinuclear antibodies (ANA) andanti-DNA antibodies were detected by indirect immuno-fluorescence using as substrate HEp-2 cells and Crithidialuciliae, respectively. Anti–extractable nuclear antigen an-tibodies were detected by counterimmunoelectrophoresis;serum complement fractions C3 and C4 and C-reactiveprotein were detected by nephelometry. Anticardiolipinantibodies were detected by enzyme-linked immunosor-bent assay (ELISA), and lupus anticoagulant was detectedby Russell viper venom time assay.

SLE activity was measured by European Consensus Lu-pus Activity Measure (ECLAM) score (36), modified forpregnancy. We changed 3 of 12 ECLAM items as follows:in item number 9 we considered proteinuria, �500 mg/

day, only after preeclampsia was ruled out; non-hemoliticanemia (item number 10) was not considered due to itshigh frequency during pregnancy; and, in item number 11,erythrocyte sedimentation rate (ESR) was not consideredbecause it usually increases during pregnancy, mainly dueto anemia and hemodilution.

The laboratory and clinical findings of our patients atconception are summarized in Table 1. For the purpose ofthis study, we considered only those pregnancies thatended in live birth. Data regarding pregnancy outcome areshown in Table 2.

Hormone assays. Serum samples for hormone testingwere collected in the following periods: within the 3months prior to pregnancy in the 12 planned pregnancies;at 9, 17, and 29 weeks of pregnancy; and at 1 month afterdelivery in all cases. All serum samples were taken at 8:00AM and kept frozen until the hormone assays were per-formed.

Serum concentrations of cortisol (ng/ml), 17�-estradiol(estradiol; pg/ml), progesterone (ng/ml), and testosterone(ng/ml) were determined by chemiluminescence assay(Immulite, Diagnostic Product Corporation, Los Angeles,CA; sensitivity: cortisol 2 ng/ml, estradiol 10 pg/ml, pro-gesterone 0.2 ng/ml, testosterone 0.1 ng/ml). DHEAS (�g/dl) was assayed by ELISA (Biochem Immunosystems Ita-lia, Bologna, Italy; sensitivity: 5 �g/dl).

Statistical analysis. Programs from the BMDP statisticalpackage (37) were used for calculations. A two-tailed ana-lysis was used. The analysis of variance (ANOVA) for

Table 2. Outcomes of SLE pregnancies*

Patientnumber

Flare(week ofgestation)

Prednisonemean dailydosage (mg)

Obstetricalproblems

Deliveryweek

Fetalproblems

Apgar index(1st/5th min)

Newbornweight (g)

Placentaweight (g)

1 Proteinuria (22) 28 None 36 Prematurity 9/10 2,660 4502 Rash (16) 19.4 Postpartum

uterine athony(subtotalhysterectomy)

38 None 9/10 3,400 800

3 None 0 None 40 None 9/10 3,300 6104 Convulsion (1 pp) 13.3 Oligohydramnios 38 Unicum atrium 8/9 2,850 5205 Arthritis (3 pp) 5 Preeclampsia 37 None 9/10 2,430 6106 None 10 Preeclampsia 37 None 9/10 2,250 4407 None 5 None 40 None 9/10 3,170 5808 None 12.5 PPROM 36 Prematurity 8/9 2,850 4509 Lymphopenia (7) 3.6 Hypercontractility 35 Prematurity,

hypotonia,hypoglycemia

4/7 2,380 370

10 Proteinuria (20) 0 None 40 None 9/9 3,360 55011 None 5 None 40 None 9/10 2,950 40012 Proteinuria (20) 15.5 PROM 38 None 10/10 2,670 65013 None 18.6 None 38 None 9/10 3,700 62014 None 5 None 39 None 9/10 3,370 61015 None 0 Preeclampsia 37 None 9/10 2,650 57016 None 15 None 33 Prematurity 8/9 2,400 42017 None 10 Oligohydramnios 33 Prematurity 9/10 2,300 400

SLE � systemic lupus erythematosus; pp � postpartum; PROM � premature rupture of membranes; PPROM � precocious preterminal rupture ofmembranes.

204 Doria et al

repeated measures was performed on protocol variables,considering the periods of data collection as within-sub-ject factors and clinical classification as grouping factors.Within-group contrasts were performed according to Bon-ferroni’s method. Results of ANOVA are presented report-ing 3 F test values, namely FG for grouping factor, FT fortime, and FGXT for the interaction between time and group-ing factors. The BMDP program 6D was used for linearcorrelation and regression analysis.

RESULTS

Because most of the pregnancies (70%) were planned onthe basis of inactive disease, the patient mean ECLAMscore at conception was found to be substantially low(Table 1). However, the disease was moderately active atconception in 3 of 5 patients in whom pregnancy unex-pectedly occurred (cases 4, 5, and 8; Table 1). Seven pa-tients had a flare during pregnancy or postpartum (41%): 2with unexpected and 5 with planned pregnancy. Fiveflares were observed in the second trimester and 2 in thepostpartum period. Disease activity according to theECLAM score varied significantly during pregnancy andpostpartum (F � 2.88, P � 0.05), being higher in thesecond trimester and the postpartum period and lower inthe third trimester (Figure 1). We also observed a signifi-cant variation of some hematologic and immunologic pa-rameters during pregnancy and postpartum. Leukocytecount was higher, and � globulins and ANA titer werelower in the third compared with the second trimester andpostpartum (Table 3).

No patients had active renal disease at conception andall had normal renal function before pregnancy, through-

out pregnancy, and postpartum. However, we observedproteinuria in 3 cases, all during the second trimester.

All but 3 patients were taking prednisone throughoutpregnancy and postpartum. The dosage was maintained inthose patients in whom the disease did not flare and wasincreased in those who relapsed, in order to control SLEactivity. Thereafter, the dosage was soon tapered to theminimal possible dosage. Two patients were taking anti-malarial drugs and one was taking cyclosporin A duringthe pregnancy. In one patient (number 10; Table 1), mildproteinuria was first diagnosed as preeclampsia and notherapy was introduced. Because proteinuria persisted for1 year after delivery, the patient underwent renal biopsythat showed mesangial glomerulonephritis (World HealthOrganization class II).

Hormones. Within the 3 months before pregnancy,among the steroid hormones tested, only DHEAS meanlevels were significantly lower in SLE patients comparedwith healthy women (Table 4)

Serum levels of all steroids varied significantly duringpregnancy and postpartum, both in the patients andhealthy controls, as expected (Figures 2–4): DHEAS (FT �9.6, P � 0.002), testosterone (FT � 7.0, P � 0.0019), estra-diol (FT � 46.4, P � 0.0001), progesterone (FT � 31.2, P �0.0001), and cortisol (FT � 26.2, P � 0.0001).

Some noteworthy and relevant differences in steroidhormone levels and profiles between patients and healthycontrols were observed. Total levels of DHEAS (Figure 2)the adrenal androgen with immunosuppressive activity,were significantly lower in patients compared with preg-nant controls throughout gestation (FG � 9.7, P � 0.0049),although the hormone level profile was similar in bothgroups. Conversely, total serum testosterone concentration(the gonadal androgen with immunosuppressive activi-ties) and its concentration profile during pregnancy didnot differ between SLE patients and controls (Figure 2).

Estradiol level (Figure 3) showed the most relevantchange in patients versus controls. Its concentration wassignificantly reduced in SLE patients, particularly in thethird trimester of pregnancy (FG � 34.5, P � 0.0001),leading to a completely different profile compared withhealthy pregnant subjects (FGXT � 12.5, P � 0.0001). Theprogesterone levels were found to be significantly reducedin patients compared with controls (FG � 11.3, P � 0.0027)and the hormone level profile (Figure 3) was also different(FGXT � 12.5, P � 0.0001). The total serum cortisol levels(Figure 4) were similar in both patients and controls; how-ever, the hormone concentration during pregnancy varied

Table 3. Hematologic and immunologic parameters (mean � SD) during pregnancy and postpartum in 17 SLE patients*

First trimester Second trimester Third trimester Postpartum F P

Leukocytes (n � 109/liter) 5.67 � 1.78 6.72 � 2.24 7.60 � 2.52 5.72 � 2.12 11.23 �0.0001Lymphocytes (n � 109/liter) 1.39 � 0.50 1.34 � 0.46 1.52 � 0.58 1.72 � 0.60 8.10 0.0002Gamma globulins (g/liter) 13.87 � 3.92 11.51 � 2.72 10.62 � 2.99 13.71 � 3.18 13.62 �0.0001ANA titer 1,922 � 2,481 1,668 � 2,359 1,498 � 2,381 1,536 � 2,371 2.86 0.0464

* SLE � systemic lupus erythematosus; ANA � antinuclear antibodies.

Figure 1. European Consensus Lupus Activity Measure (ECLAM)score fluctuation during pregnancy in 17 systemic lupus erythem-atosus patients.

Hormones in Lupus Pregnancy 205

significantly between the two groups (FGXT � 6.3, P �0.0019).

To verify the possibility that sex hormone alterationsmight have been influenced by concomitant corticosteroidtreatment, the patients were subdivided into 2 groups: thefirst group included 8 patients (3 of whom were steroid-free) who were taking a prednisone dosage of �5 mg/day(mean � SD, 3 � 2.5 mg/day), the second group included9 patients who were taking �5 mg/day (mean � SD, 16 �5.6 mg/day). A comparison of steroid hormone levels didnot show any differences between SLE patients and con-trols, apart from cortisol concentration (Figure 4) that, asexpected, was significantly reduced in SLE patients takinga prednisone dosage of �5 mg/day (FG � 4.9, P � 0.042).

However, when SLE patients treated with prednisone at�5 mg/day (including 3 not treated) were compared withthe control group, the differences for all hormone concen-trations were less evident than between overall SLE pa-tients and healthy women, as expected (Figures 2–4).

We did not observe any correlation between steroidhormone concentrations and ECLAM score, leukocyte andlymphocyte count, gamma globulin, IgG, IgA, IgM, andANA titer, within any distinct gestational period.

DISCUSSION

Pregnancy is a condition during which the steroid hor-mone system undergoes profound changes, and is an op-timum physiologic dynamic model to investigate thesteroid hormone balance and steroid-induced immuno-modulation in terms of clinical evolution of immune-me-diated diseases.

Up to now, just one prospective study has been pub-lished concerning steroid hormone levels in relation todisease activity in pregnant women with SLE (38). In thisstudy, prolactin was increased, whereas estrogens and tes-tosterone were reduced throughout pregnancy in 9 SLEpatients compared with 9 healthy and 5 RA subjects.These abnormalities seemed more relevant in patientswith active disease. However, data regarding steroid hor-mone levels, and on progesterone, DHEAS, and cortisollevels before pregnancy and postpartum were lacking.

In our study, the steroid hormone setting before preg-nancy did not differ in SLE compared with healthy sub-jects, apart from DHEAS serum levels, which were mark-

Table 4. Hormone levels (mean � SD) before pregnancyin SLE patients and healthy controls*

SLEpatients(n � 12)

Healthysubjects(n � 8) P

DHEAS (�g/dl) 86.38 � 67.68 231.50 � 71.13 �0.0001Testosterone

(ng/ml)0.19 � 0.18 0.27 � 0.15 NS

17�-estradiol(pg/ml)

0.11 � 0.07 0.07 � 0.03 NS

Progesterone(ng/ml)

3.50 � 4.38 3.83 � 5.55 NS

Cortisol (ng/ml) 93.20 � 51.61 122.42 � 44.19 NS

* SLE � systemic lupus erythematosus; DHEAS � dehydroepi-androsterone sulfate.

Figure 2. Dehydroepiandrosterone sulfate (DHEAS) and testosterone serum levels during pregnancy and postpartum in systemic lupuserythematosus (SLE) patients and in healthy controls.

206 Doria et al

edly decreased in SLE patients. According to someinvestigators (2), the DHEAS low level in SLE is due toadrenal hypofunction; alternatively, it could be the conse-quence of a DHEAS abnormal metabolism.

In addition, significant variations of steroid hormonelevels were observed both in SLE patients and controlsthroughout pregnancy, as expected. However, several ste-roid hormone alterations, in terms of concentration orlevel profile, were found in SLE patients only, suggestingthat endogenous steroid production or metabolism aremarkedly impaired in SLE during pregnancy and postpar-tum. Steroid hormone imbalance does not seem to be

related to corticosteroid treatment, apart from cortisol lev-els, which as expected, were significantly lower in patientstaking prednisone at a mean dosage �5 mg/day comparedwith controls (Figure 4).

Therefore the significant persisting decrease in DHEASconcentration observed in SLE patients suggests that adre-nal hypofunction and/or hormone abnormal metabolismin SLE is maintained even during pregnancy.

Estradiol and progesterone showed the most relevantalterations in that both were significantly lower than ex-pected in pregnant women with SLE in the second andeven more in the third trimester, periods in which these

Figure 3. 17�-estradiol and progesterone serum levels during pregnancy and postpartum in systemic lupus erythematosus (SLE) patientsand healthy controls.

Figure 4. Cortisol serum levels during pregnancy and postpartum in 17 systemic lupus erythematosus (SLE) patients and in 10 healthycontrols.

Hormones in Lupus Pregnancy 207

hormones are predominantly secreted by the placenta (12).Thus, the reduction in their serum concentration mightsuggest placental damage or dysfunction. In fact, placentalchanges or insufficiency related to a decidual vasculopa-thy/coagulopathy and/or chronic villitis of unknown eti-ology are frequently reported in SLE pregnancies, even inthe absence of ascertained risk factors, such as antiphos-pholipid antibodies (39). Alternatively, the findings couldbe due to a placental metabolism abnormality.

Generally, the most relevant immunologic effect of hor-monal modifications in normal pregnancy seems to be asteroid-induced Th2 cytokine polarization (10), i.e., a pro-gressive inhibition of cellular immunity with the conse-quent enhancement of humoral immunity and antibodyproduction (5–7,10,40–43). Given that the immune re-sponse in SLE is considered to be Th2 cytokine driven (44)because of the overexpression of Th2-type cytokines, inparticular IL-10 (45–47), a disease flare in pregnant pa-tients affected by SLE would be expected, particularly inthe third trimester. However, several recent prospectivestudies reported a low percentage of flares in the thirdtrimester of SLE pregnancy (22,27,31–34), and our data areconsistent with such recent reports showing a disease ac-tivity increase in the second trimester and during thepostpartum period (Figure 1).

Therefore, the lower than expected increase in estradioland progesterone production observed during the thirdtrimester in SLE patients might account for the reducedSLE activity reported in the same gestational period, prob-ably related to the decreased hormone-induced Th2 im-mune response. In other words, a placental compromiseand related reduced hormonal synthesis could be protec-tive against a flare of the disease in SLE pregnant patients,together with the still-evident increase of testosterone, anatural immunosuppressor.

In summary, a dysregulation in steroid hormone produc-tion occurs in SLE and becomes more evident during preg-nancy. Both gonadal and adrenal hormone levels are re-duced during pregnancy in SLE patients compared withhealthy controls. The major hormonal alteration observedwas an unexpected lack of estrogen (and to a lesser extentprogesterone) serum level increase during the secondand—even more—the third trimester of gestation, proba-bly due to placental compromise. Therefore, these steroidhormone variations may result in a lower humoral im-mune activation, probably related to a change in the estro-gen/androgen balance, that in turn could account for thedecrease in disease activity observed during the third tri-mester in pregnant SLE patients.

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