|Year : 2018 | Volume
| Issue : 3 | Page : 117-123
Influence of prolactin and estrogen on disease activity in patients with systemic lupus erythematosus
Marwa Mahmoud Abdelaziz1, Samar H Goma1, Sohair K Sayed2, Dina H El-Hammady3, Rania M Gamal4, Doaa Samir Sayed5
1 Lecturer of Rheumatology and Rehabilitation, Faculty of Medicine, Assiut University, Assiut, Egypt
2 Assistant Professor of Clinical Pathology, Faculty of Medicine, Assiut University, Egypt
3 Assistant Professor of Rheumatology and Rehabilitation, Faculty of Medicine, Helwan University, Egypt
4 Assistant Professor of Rheumatology and Rehabilitation, Faculty of Medicine, Assiut University, Egypt
5 Assistant professor of Dermatology and Venereology, Faculty of Medicine, Assiut University, Egypt
|Date of Submission||07-Apr-2017|
|Date of Acceptance||05-Aug-2017|
|Date of Web Publication||18-Jul-2018|
Samar H Goma
Assiut University, Assiut
Source of Support: None, Conflict of Interest: None
Objective The objective of this paper is to evaluate the role of prolactin and estrogen levels on disease activity in patients with systemic lupus erythematosus (SLE).
Patients and methods This study included 60 female patients with SLE, with a mean age of 33.5±13.12 years. It was conducted between November 2014 and October 2015. Disease activity was defined according to Systemic Lupus Erythematosus Activity Index; score of at least 6 was considered as an active disease. Prolactin (PRL) and estrogen levels and other serological markers of lupus disease activity, namely, complement 3,4 (C3 and C4), erythrocyte sedimentation rate, C-reactive protein, and anti-double-stranded DNA (anti-dsDNA) titer were calculated.
Results Hyperprolactinemia was present in 25.0% of patients, and low estrogen level was present in 33.3% of patients. There was no significant correlation between either of estrogen or prolactin levels and all clinical and laboratory features, except for a significant positive correlation between anti-dsDNA and hyperprolactinemia.
Conclusion There was no significant correlation between either of PRL or estrogen levels and Systemic Lupus Erythematosus Activity Index score. Overall, 80.0% of patients with hyperprolactinemia and 80.0% with low estrogen level had SLE activity. There was a significant difference in the frequency of further indicators of disease activity in SLE such as raised erythrocyte sedimentation rate, raised C-reactive protein, or decrease in complement factors with high serum PRL and low estrogen level.
Keywords: estrogen, prolactin, Systemic Lupus Erythematosus Activity Index, systemic lupus erythematosus
|How to cite this article:|
Abdelaziz MM, Goma SH, Sayed SK, El-Hammady DH, Gamal RM, Sayed DS. Influence of prolactin and estrogen on disease activity in patients with systemic lupus erythematosus. Egypt Rheumatol Rehabil 2018;45:117-23
|How to cite this URL:|
Abdelaziz MM, Goma SH, Sayed SK, El-Hammady DH, Gamal RM, Sayed DS. Influence of prolactin and estrogen on disease activity in patients with systemic lupus erythematosus. Egypt Rheumatol Rehabil [serial online] 2018 [cited 2020 Feb 21];45:117-23. Available from: http://www.err.eg.net/text.asp?2018/45/3/117/237044
| Introduction|| |
Systemic lupus erythematosus (SLE) is a potentially fatal and severe chronic autoimmune disease that affects multiple organ systems. It is remarkably heterogeneous, with diverse and dynamic symptoms manifested by flares of disease activity . Hormonal, infectious, and environmental factors have been implicated in the etiology of the disease .
SLE is a disease of young women, which occurs from infancy to old age, with peak occurrence between ages 15 and 40 years. Females are affected far more than males (6–10 : 1) ,. It seems highly plausible that female sex hormones contribute to the pathogenesis of lupus based on the tendency for disease onset during the child-bearing years , increased numbers of flares during high hormonal states such as pregnancy  and ovulation-induction therapy, and remissions after menopause . It has been proved that steroid hormones such as 17 β-estradiol, testosterone, prolactin, progesterone, and dehydroepiandrosterone influence immune system regulation , and the activity of SLE .
Prolactin (PRL) participates in a number of important functions in the body: performs as a hormone, mainly owing to its pituitary production, and acts as a cytokine. Prolactin is also secreted by immune cells and its receptor belongs to the family of cytokine receptors type 1 , and it may play a role in the pathogenesis and clinical activity of SLE and other autoimmune diseases in human and experimental animal models . PRL secretion is inhibited by the hypothalamus through dopamine. Thyroid-releasing hormone, hypothyroidism, and adrenal insufficiency stimulate PRL secretion by inhibiting dopamine secretion. The main cytokines stimulating PRL secretion are interleukin (IL)-1, IL-2, and IL-6, whereas interferon-γ and endothelin 3 are inhibitory .
The prevalence of hyperprolactinemia in the general population is lower than 5%. Nevertheless, the average prevalence of hyperprolactinemia in patients with lupus is 20–30%, varying from 8 to 69.7% . There is controversy about the existence of a correlation between the disease activity and the concentration of serum PRL in SLE. Some authors reported these two parameters to be positively correlated ,, whereas others denied an association ,.
In the classical mechanism of steroid hormone action, estradiol diffuses into target cells and binds to estrogen receptors located in the nucleus. The ligand-activated receptors interact at specific DNA sites, termed estrogen response elements, along target genes and alter the rate of transcription . Estradiol can both activate and repress genes within a given signal transduction pathway contributing to abnormal signal transduction in SLE T cells . Grimaldi et al.  found that estrogens play an important role in B-cell maturation, selection, and activation and, thus, can potentially weaken the immune system. There are conflicting opinion in the literatures about the influence of estrogens on the development of SLE ,,,,.
We aimed in this study to evaluate the role of PRL and estrogen levels on disease activity in patients with SLE.
| Patients and methods|| |
This was a cross-sectional study, conducted between November 2014 and October 2015. It included 60 female patients with SLE aged from 16 to 58 years with a mean age of 33.5±13.12 years who were diagnosed according to the American College of Rheumatology Criteria . The study was carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients.
Demographic characteristics, clinical manifestations, and autoantibody profile such as anti-double-stranded DNA (anti-dsDNA) were recorded. Disease activity was defined according to Systemic Lupus Erythematosus Activity Index (SLEDAI) ; score of at least 6 was considered as an active disease.
Besides clinical assessment, venous blood was taken for measurement of the PRL, estrogen levels, and other serological markers of lupus disease activity, namely, C3, C4, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and anti-dsDNA titer.
Patients with renal and/or hepatic failure, pregnancy, lactation, hypothyroidism, taking medications known to affect PRL level, or taking sex hormones (oral contraceptives, hormone replacement, etc.) were excluded from the analysis.
The patients under investigation were fasting. Overall, 10 ml of venous blood was taken from all patients between 8:00 and 10:00 AM and divided into the following: 3 ml in sterile EDTA-containing tubes for complete blood counts (CBC), 1.6 ml in tubes containing 3.8% sodium citrate for ESR, and the remainder was left in plain tubes for spontaneous clotting at room temperature before being centrifuged at 3000 rpm for 10 min. Serum samples were kept at −20°C for the hormonal determination (PRL and estrogen) and further analysis.
Kidney and liver function tests and lipid profile were performed using a chemical analyzer Hitachi 911 (Boehringer Mannheim, Germany). CBC was detected by Beckman Coulter (Brea, California, USA) HMX. ESR was performed using Westergren method.
Complete urine analysis was done by reagent strip 10 parameters (Polypharma, Boulevard de la réunification DOUALA, CAMEROON), whereas protein in 24 h urine was measured on COBAS Integra 400 autoanalyzer (Roche, Grenzacherstrasse, Basel, Switzerland) and creatinine clearance was calculated .
C3 and C4 serum level was assessed using BN Prospec System (Siemens Healthcare GmbH, Henkestr, Erlangen, Germany). Anti-dsDNA IgG autoantibodies were performed by Alegria, LongfieldKent, England, DiaSorine, Stillwater, Minnesota, USA. Antinuclear antibodies (ANAs) were determined by the indirect immunofluorescence technique on Hep2 cells (HEP2 cell line substrate; Dia Sorine). C-reactive protein was detected by latex agglutination test kit (Biotec Laboratories Ltd, Dorset, UK). PRL and estrogen levels were detected by VIDAS (Biomérieux, Marcy l’Etoile, France).
Data were analyzed using the statistical package SPSS, version 21. Data were expressed as mean±SD, median, and frequencies. Group differences were compared by using t-test, one-way analysis of variance, ×2, Mann–Whitney U-test, and Fisher’s exact test when applicable. Pearson’s correlation coefficient (r) between variables was calculated.
Linear regression analysis was performed. Serum PRL level was used as the dependent variable. Probability levels below 0.05 were considered significant.
| Results|| |
In this study, 60 female patients with SLE were included. The mean age was 33.5±13.12 (range: 17–58) years, and the mean duration of the disease was 5.23±2.87 (range: 0.50–16) years. The mean PRL level of all patients was 19.55±12.59 (range 4.70–70.6) ng/ml. The mean estrogen level of all patients was 57.9±65.7 (range: 13.4–284.8) pg/ml.
Hyperprolactinemia (defined as a level>25 ng/ml) was present in 15/60 (25%) patients.
Low estrogen level (defined as a level<25 pg/ml) was present in 20/60 (33.3%) patients. There were menstrual disturbances in 40/60 (66.6%) patients. We had 20 (33.3%) patients with low estrogen level, 40 (66.7%) patients with normal estrogen level, but no patients with high estrogen level.
[Table 1] shows the demographic and clinical features of the normoprolactinemic and hyperprolactinemic groups of patients. Nonsignificant difference was observed between normal and hyperprolactinemic groups regarding different clinical features such as photosensitivity, malar rash, discoid rash, oral ulcers, arthralgia, arthritis, pluritis, nephritis, pericarditis, and central nervous system manifestations (P>0.05).
|Table 1 Clinical features of SLE patients in normal and hyperprolactinemia|
Click here to view
[Table 2] shows the laboratory and serological profiles of the normoprolactinemic and hyperprolactinemic groups of patients and SLEDI score. There was no significant correlation between PRL level and red blood cells, white blood cells, platelets, hemoglobin level, 24H protein, and creatinine clearance. However, a significant positive correlation was observed with anti-dsDNA (r=0.387, P<0.05). Correlation was also tested between the PRL level and other serological markers of lupus activity. Again, no significant correlation could be demonstrated between PRL level and C3 (r=0.234, P=0.190), C4 (r=0.208, P=0.531), and ESR (r=0.277, P=0.124). On the basis of SLEDAI, 45/60 (75%) patients were identified with lupus activity (SLEDAI≥6); there was no significant correlation between PRL level and SLEDAI score (r=0.177, P=0.323). Overall, 12/15 (80%) patients with hyperprolactinemia had SLE activity.
|Table 2 Laboratorial features of SLE patients in normal and hyperprolactinemia|
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[Table 3] shows the demographic and clinical features of the groups of patient with normal and low estrogen level. There was no significant correlation between the estrogen level and all clinical features (P>0.05). [Table 4] shows the laboratory and serological profiles of the normal and low estrogen groups of patients and SLEDAI score. There was no significant correlation between estrogen level and red blood cells, white blood cells, platelets, hemoglobin level, 24H protein, creatinine clearance, and anti-dsDNA.
Correlation was also tested between the estrogen level and other serological markers of lupus activity. Again, no significant correlation could be demonstrated between estrogen level and C3, C4, and ESR. There was no significant correlation between estrogen level and SLEDAI score. Overall, 16/20 (80%) of low estrogen patients had SLE activity.
There was a significant difference in the frequency of several clinical manifestations and serological parameters between patients with SLE with normoprolactinemia and hyperprolactinemia (malar rash, discoid rash, nephritis, pluritis, pericarditis, and central nervous system manifestations). Also, there was a significant difference in the frequency of several clinical manifestation parameters between patients with SLE with normal and low estrogen level (malar rash, oral ulcers, arthralgia, arthritis, pericarditis, and elevation of CRP). Low complement appeared to be more common in hyperprolactinemic and in low estrogen groups, although the difference did not reach statistical significance.
| Discussion|| |
SLE is a complex autoimmune disorder that develops in genetically prone individuals under the influence of various environmental factors. It is an autoimmune disease with a wide array of clinical manifestations. It is characterized by the production of antibodies to components of the cell nucleus ,. We aimed in this study to evaluate the role of prolactin and estrogen levels on disease activity in patients with SLE.
Hyperprolactinemia in patients with SLE may be caused by either enhanced secretion of pituitary PRL under the effect of inflammatory cytokines  or increased production of PRL by peripheral lymphocytes . The immune complexes of PRL-anti-PRL (which are the macroprolactins) are not biologically active, as their large size interferes with transversing the capillary walls to reach target tissues. Delayed clearance of the PRL–IgG complex may account for increased serum levels of PRL in these patients . A high number of patients with SLE were found to be hyperprolactinemic , but there is a controversy about the existence of a correlation between disease activity and the concentration of serum PRL in patients with SLE.
Most studies point to a positive correlation between PRL and SLE activity ,,. Yang et al.  proved that the serum level of PRL was increased in the patients with active SLE compared with patients with inactive SLE and that the serum level of PRL was closely related to SLE disease activity. In the study by Zahra et al. , mild to moderately elevated PRL levels were found in 10/30 (33.3%) of patients with SLE, and there was significant association between high PRL levels and clinical disease activity. Jacobi et al.  in their study revealed a positive correlation of the disease activity and the serum PRL concentration in patients with SLE. Patients with high disease activity had significantly higher serum PRL levels compared with patients with less active disease.
Other studies denied an association between PRL and SLE activity ,. In a study by Pauzner et al. , mild hyperprolactinemia was found in 20/82 (24%) patients, and no association between hyperprolactinemia and clinical disease activity could be demonstrated. The study by Mansoor et al.  reveled that there was no significant correlation between serum PRL levels and SLEDAI and other serological disease markers, namely C3, C4, and ESR. These disagreeing results about the correlation between PRL and SLE activity can be explained by the heterogeneity of the groups of patients studied, by the use of different index to measure SLE activity, by the inclusion of patients with variable disease duration and by the diverse methodologies used for PRL testing. The presence of hyperprolactinemia is associated with diverse autoantibodies like antinuclear antibody, anti-dsDNA, anticardiolipin and antimicrosomal .
In our study, there was no significant correlation between PRL level and SLEDAI score (r=0.177, P=0.323). However, 12/15 (80%) patients with hyperprolactinemia and 34/45 (75.5%) patients with normoprolactinemia had SLE activity.
Antibodies directed toward nuclear antigens are characteristic of SLE, whereas anti-dsDNA antibodies are the hallmark for the disease . Another finding suggesting a relationship between the serum PRL concentration and the disease activity in SLE is the positive correlation between the PRL level and the concentration of anti-dsDNA (IgG) . Neidhart et al.  have shown these autoantibodies to be positively correlated with the serum PRL concentration in patients with SLE. In addition, Miranda et al.  reported a trend of anti-dsDNA-positive patients with lupus nephritis to be hyperprolactinemic compared with those who did not have anti-dsDNA antibodies. Zahra et al.  demonstrated that hyperprolactinemia in a subset of their patients correlated with high serum level of anti-dsDNA. Yang et al.  showed that increased serum levels of PRL were related to immunoglobulin and anti-ds-DNA antibody production. After treatment, the serum level of PRL was decreased with the reduction in the anti-ds-DNA antibody titer. This suggest that serum PRL might affect B-cell activation and antibody production, and that PRL might be implicated as a modulator of humoral immunity. Zhu et al.  showed a positive correlation in serum PRL levels and specific antibodies against dsDNA.
In our study, a significant positive correlation was observed between the serum PRL concentration with anti-dsDNA (r=0.387, P<0.05).
In addition, in the study by Jacobi et al. , the frequency of further indicators of disease activity in SLE, such as raised ESR or decrease in complement factors, was associated with high serum PRL.
In the study by Zhu et al. , a negative correlation was found between serum PRL levels and complement component C3.
In our study, there was a significant difference in the frequency of further indicators of disease activity in SLE such as raised ESR, raised CRP, or decrease in complement factors between normoprolactinemic and hyperprolactinemic patients.The influence of estrogens on the development of SLE remains unclear. Some studies underline the negative influence of these hormones on the immune system ,,,, especially in patients with some genetic predisposition ,, whereas others show the positive influence on health ,. In one study, the hormonal replacement therapy was associated with SLE development. No association was found when analyzing the risk for SLE among oral contraceptive users . Others studies have reported that there was a group of female affected with SLE in which the use of hormonal replacement therapy or oral contraceptive did not cause SLE exacerbation, but in a few number of patients with SLE, it did ,. There are different opinions about the disease activity influence on ovarian function. Some studies stressed the relationship between SLE activity and menstrual cycle disturbances; in other studies, this fact was not confirmed ,. In patients with SLE, the aromatic hydroxylase activity was found to be increased, which may partially explain the abnormalities of peripheral estrogen metabolism observed in these patients . Concerning serum 17 β-estradiol (E2), its levels were reported to be in increased, normal, or low in patients with SLE ,. In the study by Shabanova et al. , the decrease of E2 level was dominant, and only in 2% of patients, its increase was observed. An investigation from Munoz et al.  obtained similar results: in SLE women during luteal phase of menstrual cycle, progesterone and E2 levels were decreased.
In our study, there were menstrual disturbances in 40/60 (66.6%) patients. We had 20 (33.3%) patients with low estrogen level, 40 (66.7%) patients with normal estrogen level, but no patients with high estrogen level.
There was no significant correlation between estrogen level and SLEDAI score; however, 16/20 (80%) of low estrogen patients and 30/40 (75%) of normal estrogen patients had SLE activity.
There was a significant difference in the frequency of further indicators of disease activity in SLE such as raised ESR, raised CRP, or decrease in complement factors between patients with normal and low estrogen level.
In conclusion, this study demonstrate that no significant correlation existed between either of hyperprolactinemia or estrogen level and SLE disease activity. However, 80% of hyperprolactinemic and 80% of low estrogen patients had SLE activity.
There was a significant difference in the frequency of further indicators of disease activity in SLE such as raised ESR, raised CRP, or decrease in complement factors with high serum PRL and low estrogen level, and a significant positive correlation was observed between anti-dsDNA and hyperprolactinemia.
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| References|| |
Rahman A, Isenberg DA. Systemic lupus erythematosus. New Engl J Med 2008; 358:929–939.
Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003; 56:481–490.
Pisetsky DS, Buyon JP, Manzi S. Systemic lupus erythematosus. In: Klippel JH, Crofford LJ, Stone JH, Weyand CM, editors. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation; 2001. pp. 329–346.
Rus V, Hajeer A, Hochberg MC. Systemic lupus erythematosus. In: Silman AJ, Hochberg MC, editors. Epidemiology of the rheumatic disease. 2nd ed. New York, NY: Oxford University Press; 2001. pp. 31–71.
Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Seriolo B et al.
Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 2004; 13:635–638.
Casoli P, Tumiati B, La Sala G. Fatal exacerbation of systemic lupus erythematosus after induction of ovulation. J Rheumatol 1997; 24:1639–1640.
Guballa N, Sammaritano L, Schwartzman S, Buy J, Lockshin M. Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome. Arthritis Rheum 2000; 43:550–556.
Grimaldi CM, Hill L, Xu X, Peeva E, Diamond B. Hormonal modulation of B cell development and repertoire selection. Mol Immunol 2005; 42:811–820.
Vera-Lastra O, Jara LJ, Espinoza LR. Prolactin and autoimmunity. Autoimmun Rev 2002; 1:360–364.
Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebocontrolled trial. Arthritis Rheum 2002; 46:2924–2927.
Peeva E, Michael D, Cleary J, Rice J, Chen X, Diamond B. Prolactin modulates the naive B cell repertoire. J Clin Investig 2003; 11:275–283.
Walker SE, Jacobson JD. Roles of prolactin and gonadotrophinreleasing hormone in rheumatic diseases. Rheum Dis Clin North Am 2000; 26:713–736.
Chikanza IC. Prolactin and neuroimmunomodulation: in vitro and in vivo observations. Ann NY Acad Sci 1999; 876:119–130.
Vera-Lastra O, Mendez C, Jara LJ, Cisneros M, Medina G, Ariza R et al.
Correlation of prolactin serum concentrations with clinical activity and remission in patients with systemic lupus erythematosus. Effect of conventional treatment. J Rheumatol 2003; 30:2140–2146.
Neidhart M. Elevated serum prolactin or elevated prolactin/cortisol ratio are associated with autoimmune processes in systemic lupus erythematosus and other connective tissue diseases. J Rheumatol 1996; 23:476–481.
El-Garf A, Salah S, Shaarawy M, Zaki S, Anwer S. Prolactin hormone in juvenile systemic lupus erythematosus: a possible relationship to diseaese activity and CNS manifestations. J Rheumatol 1996; 23:374–377.
Mok CC, Lau CS, Tam SC. Prolactin profile in a cohort of Chinese systemic lupus erythematosus patients. Br J Rheumatol 1997; 36:986–989.
Buskila D, Lorber M, Neumann L, Flusser D, Shoenfeld Y. No correlation between prolactin levels and clinical activity in patients with systemic lupus erythematosus. J Rheumatol 1996; 23:629–632.
Klinge CM. Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 2001; 29:2905–2919.
Walters E, Rider V, Abdou NI, Greenwell C, Svojanovsky S, Smith P et al.
Estradiol targets T cell signaling pathways in human systemic lupus. Clin Immunol 2009; 133:428–436.
Zandman-Goddard G, Solomon M, Rosman Z, Peeva E, Shoenfeld Y. Environment and lupus related diseases. Lupus 2012; 21:241–250.
Johansson M, Arlestig L, Moller B, Smedby T, Rantapää-Dahlqvist S. Oestrogen receptor alpha gene polymorphisms in systemic lupus erythematosus. Ann Rheum Dis 2005; 64:1611–1617.
Stavrou I, Zois C, Ioannidis JP, Tsatsoulis A. Association of polymorphisms of the oestrogen receptor alpha gene with the age of menarche. Hum Reprod 2002; 17:1101–1105.
Hochberg MC. Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35:630–640.
Rock RC, Walker WG, Jennings CD. Nitrogen metabolites and renal function. In: Tiez NW, editor. Fundamentals of clinical chemistry. 3rd ed. Philadelphia, PA: W.B. Saunders Company; 1987. pp. 669–704.
Tsigos C, Papanicolaou DA, Defensor R, Mitsiadis CS, Kyrou I, Chrousos GP et al.
Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology 1997; 66:54–62.
Jara LJ, Vera-Lastra O, Miranda JM, Alcala M, Alvarez- Nemegyci J. Prolactin in human systemic lupus erythematosus. Lupus 2001; 10:748–756.
Leanos-Miranda A, Chavez-Rueda KA, Blanco-Favela F. Biologic activity and plasma clearance of prolactin-IgG complex in patients with systemic lupus erythematosus. Arthritis Rheum 2001; 44:866–875.
Orbach H, Shoenfeld Y. Hyperprolactinemia and autoimmune diseases. Autoimmun Rev 2007; 6:537–542.
Jara LJ, Pacheco-Reyes H, Medina G, Angeles U, Cruz PC, Saavedra MA et al.
Prolactin levels are associated with lupus activity, lupus anticoagulant, and poor outcome in pregnancy. Ann NY Acad Sci 2007; 1108:218–226.
Yang J, Li Q, Yang X, Li M. Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus. Lupus 2016; 25:513–519.
Rezaieyazdi Zahra, Hesamifard Afsane. Correlation between serum prolactin levels and lupus activity. Rheumatol Int 2006; 26:1036–1039.
Jacobi AM, Rohde W, Ventz M, Riemekasten G, Burmester GR, Hiepe F. Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity. Lupus 2001; 10:554–561.
Jokar M, Tayyebi Maybodi N, Amini A, Hatef Fard M. Prolactin and macroprolactin in oatienys with systemic lupus erythematosus. Int J Rheum Dis 2008; 11:257–262.
Smiti Khanfir M, Ben Ghorbel I, Feki M, Lamloum M, Mebazaa A, Miled M et al.
Hyperprolactinemia in systemic lupus erythematosus. A prospective study of 38 cases. Tunis Med 2004; 82:512–515.
Pauzner R, Urowitz MR, Gladman DD, Gough JM. Prolactin in systemic lupus erythematosus. J Rheumatol 1994; 11:2064–2067.
Karimifar M, Tahmasebi A, Bonakdar ZS, Purajam S. Correlation of serum prolactin levels and disease activity in systematic lupus erythematosus. Rheumatol Int 2013; 33:511–516.
Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G et al.
Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann NY Acad Sci 2007; 1109:385–400.
Yung S, Chan T. Anti-DNA antibodies in the pathogenesis of lupus nephritis – the emerging mechanisms. Autoimmun Rev 2008; 7:317–321.
Miranda JM, Prieto RE, Paniagua R, Garcia G, Amato D, Barile L et al.
Clinical significance of serum and urine prolactin levels in lupus glomerulonephritis. Lupus 1998; 7:387–391.
Zhu X, Xu J, Li S, Huang W, Li F. Role of abnormal anterior pituitary hormones-growth hormone and prolactin in active systemic lupus erythematosus. Int J Clin Exp Med 2015; 8:19223–19231.
McMurray RW, May W. Sex hormones and systemic lupus erythematosus: review and meta-analysis. Arthritis Rheum 2003; 48:2100–2110.
Rojas-Villarraga A, Torres-Gonzalez JV, Ruiz-Sternberg AM. Safety of hormonal replacement therapy and ora contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis. PLoS One 2014; 19:9.
Quintero OL, Amador-Patarroyo MJ, Montoya-Ortiz G, Rojas-Villarraga A, Anaya JM. Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. J Autoimmun 2012; 38:109–119.
Schwarz EB, Lohr PA. Oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2006; 354:1203–1204.
Cabral de sousa D, Das Chagas MM, Trindade VS, Salani RM. Anti-corpus luteum antibody and menstrual irregularity in patients with systemic lupus erythematosus and Hashimoto’s thyroiditis. Lupus 2005; 14:618–624.
Brunner HI, BishnoiI A, Barron AC, Houk LJ, Ware A, Farhey Y et al.
Disease outcomes and ovarian function of childhood-onset systemic lupus erythematosus. Lupus 2006; 15:198–206.
Cutolo M, Capellino S, Sulli A, Serioli B, Secchi ME, Villaggio B et al.
Estrogens and autoimmune diseases. Ann NY Acad Sci 2006; 1089:538–547.
Munoz JA, Gil A, Lopez-Dupla JM, Vazguez JJ, Gonzales Gancedo P. Sex hormones in chronic systemic lupus erythematosus. Ann Med Interne 1994; 145:459–463.
Shabanova SS, Ananieva LP, Alekberova ZS, Guzov II. Ovarian function and disease activity in patients with systemic lupus erythematosus. Clin Exp Rheumatol 2008; 26:436–441.
[Table 1], [Table 2], [Table 3], [Table 4]