Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Graft-Versus-Host Disease

Androgens in women after allogeneic hematopoietic cell transplantation: impact of chronic GvHD and glucocorticoid therapy

Bone Marrow Transplantation volume 52, pages 431–437 (2017)Cite this article

Subjects

Abstract

Low androgen levels may contribute to sexual dysfunction in women after allogeneic hematopoietic cell transplantation (alloHCT). However, data on serum androgens in women after alloHCT are limited. The aim of this study was to assess androgen levels and their association with chronic GvHD (cGvHD) and glucocorticoid (GC) therapy. Included were 65 allografted women, 33 with cGvHD, and 23 of these were on GC therapy. Controls were 94 healthy, age-matched women. Supportive study groups were women after autologous HCT (autoHCT; n=20) and non-transplanted women on GC therapy (n=26). Compared with controls, free testosterone (free T) and dehydroepiandrosterone sulfate (DHEAS) levels were lower in both the alloHCT group and GC groups; P<0.0001 and P<0.05, respectively. Androgens in the autoHCT group were similar or higher than controls. In the subgroup of alloHCT patients without cGvHD, free T was similar to controls (7.2 vs 8.6 pmol/L; P=0.42), whereas DHEAS levels was lower than controls (1.7 vs 2.5 μmol/L; P=0.008). Compared with controls, cGvHD without GC (n=10) was associated with lower free T and DHEAS; P=0.004 and P=0.0004, respectively). The lowest androgen levels were seen in women with both cGvHD and GC therapy. In conclusion, low serum androgens were associated with cGvHD and GC therapy, prompting for studies assessing a possible association between low androgens and sexual dysfunction and quality of life in allografted women.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Syrjala KL, Kurland BF, Abrams JR, Sanders JE, Heiman JR . Sexual function changes during the 5 years after high-dose treatment and hematopoietic cell transplantation for malignancy, with case-matched controls at 5 years. Blood 2008; 111: 989–996.

    Article  CAS  Google Scholar 

  2. Watson M, Wheatley K, Harrison GA, Zittoun R, Gray RG, Goldstone AH et al. Severe adverse impact on sexual functioning and fertility of bone marrow transplantation, either allogeneic or autologous, compared with consolidation chemotherapy alone: analysis of the MRC AML 10 trial. Cancer 1999; 86: 1231–1239.

    Article  CAS  Google Scholar 

  3. Noerskov KH, Schjodt I, Syrjala KL, Jarden M . Sexual function 1-year after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2016; 51: 833–840.

    Article  CAS  Google Scholar 

  4. Shalet SM, Didi M, Ogilvy-Stuart AL, Schulga J, Donaldson MD . Growth and endocrine function after bone marrow transplantation. Clin Endocrinol 1995; 42: 333–339.

    Article  CAS  Google Scholar 

  5. Hovi L, Saarinen-Pihkala UM, Taskinen M, Wikstrom AM, Dunkel L . Subnormal androgen levels in young female bone marrow transplant recipients with ovarian dysfunction, chronic GVHD and receiving glucocorticoid therapy. Bone Marrow Transplant 2004; 33: 503–508.

    Article  CAS  Google Scholar 

  6. Tauchmanova L, Selleri C, De Rosa G, Esposito M, Orio F Jr, Palomba S et al. Gonadal status in reproductive age women after haematopoietic stem cell transplantation for haematological malignancies. Hum Reprod 2003; 18: 1410–1416.

    Article  Google Scholar 

  7. Davison SL, Davis SR . Androgens in women. J Steroid Biochem Mol Biol 2003; 85: 363–366.

    Article  CAS  Google Scholar 

  8. Mooradian AD, Morley JE, Korenman SG . Biological actions of androgens. Endocr Rev 1987; 8: 1–28.

    Article  CAS  Google Scholar 

  9. Wahlin-Jacobsen S, Pedersen AT, Kristensen E, Laessoe NC, Lundqvist M, Cohen AS et al. Is there a correlation between androgens and sexual desire in women? J Sex Med 2015; 12: 358–373.

    Article  CAS  Google Scholar 

  10. Davison SL, Bell R, Donath S, Montalto JG, Davis SR . Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005; 90: 3847–3853.

    Article  CAS  Google Scholar 

  11. Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL . A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J Clin Endocrinol Metab 2000; 85: 2832–2838.

    CAS  PubMed  Google Scholar 

  12. Wierman ME, Arlt W, Basson R, Davis SR, Miller KK, Murad MH et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2014; 99: 3489–3510.

    Article  CAS  Google Scholar 

  13. Traish AM, Kang HP, Saad F, Guay AT . Dehydroepiandrosterone (DHEA)—a precursor steroid or an active hormone in human physiology. J Sex Med 2011; 8: 2960–2982 quiz 83.

    Article  CAS  Google Scholar 

  14. Rutkowski K, Sowa P, Rutkowska-Talipska J, Kuryliszyn-Moskal A, Rutkowski R . Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs 2014; 74: 1195–1207.

    Article  CAS  Google Scholar 

  15. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 2009; 15: 1628–1633.

    Article  Google Scholar 

  16. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  Google Scholar 

  17. Ankarberg-Lindgren C, Norjavaara E . Sensitive RIA measures testosterone concentrations in prepubertal and pubertal children comparable to tandem mass spectrometry. Scand J Clin Lab Invest 2015; 75: 341–344.

    Article  CAS  Google Scholar 

  18. Vermeulen A, Verdonck L, Kaufman JM . A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666–3672.

    Article  CAS  Google Scholar 

  19. Ankarberg-Lindgren C, Norjavaara E . A purification step prior to commercial sensitive immunoassay is necessary to achieve clinical usefulness when quantifying serum 17beta-estradiol in prepubertal children. Eur J Endocrinol 2008; 158: 117–124.

    Article  CAS  Google Scholar 

  20. Shimoji S, Hashimoto D, Kato K, Tujigiwa H, Akashi K, Teshima T . Graft-Versus-Host Disease targets granulosa cell of ovarian follicle and causes infertility after allogeneic hematopoietic stem cell transplantation. ASBMT meeting. Biol Blood and Marrow Transplant 2015; 21: S26–S27.

    Article  Google Scholar 

  21. Wagner AM, Beier K, Christen E, Hollander GA, Krenger W . Leydig cell injury as a consequence of an acute graft-versus-host reaction. Blood 2005; 105: 2988–2990.

    Article  CAS  Google Scholar 

  22. Grigg AP, McLachlan R, Zaja J, Szer J . Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg). Bone Marrow Transplant 2000; 26: 1089–1095.

    Article  CAS  Google Scholar 

  23. Labrie F, Luu-The V, Belanger A, Lin SX, Simard J, Pelletier G et al. Is dehydroepiandrosterone a hormone? J Endocrinol 2005; 187: 169–196.

    Article  CAS  Google Scholar 

  24. Arlt W, Justl HG, Callies F, Reincke M, Hubler D, Oettel M et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab 1998; 83: 1928–1934.

    Article  CAS  Google Scholar 

  25. Nordmark G, Bengtsson C, Larsson A, Karlsson FA, Sturfelt G, Ronnblom L . Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus. Autoimmunity 2005; 38: 531–540.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from Swedish Cancer Society (CAN 2012/387, CAN 2012/795), the Swedish state via the ALF agreement (ALFGBG 16564), the Gothenburg Medical Society and The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland. Special thanks to Maria Strömbom.

Author information

Authors and Affiliations

  1. Department of Medicine, Section of Hematology and Coagulation, Sahlgrenska University Hospital, and Sahlgrenska Academy, Gothenburg, Sweden

    Y Björk, I Andersson & M Brune

  2. Department of Obstetrics and Gynecology, NU Hospital Group, and Sahlgrenska Academy, University of Gothenburg, Trollhättan, Sweden

    E Smith Knutsson

  3. Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    C Ankarberg-Lindgren

  4. Department of Obstetrics and Gynecology, NU Hospital Group, Trollhättan, Sweden

    A-K Broman

  5. Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

    L Björkman

  6. Department of Pulmonary Medicine, Institute of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

    J Magnusson

  7. Department of Oncology, Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg, Sweden

    K Bergmark

  8. Department of Clinical Sciences Lund, Cancer Epidemiology, University of Lund, Lund, Sweden

    H Anderson

  9. Department of Medicine, Section of Hematology, South Älvsborg Hospital, and Sahlgrenska Academy, Borås, Sweden

    P-O Andersson

Authors
  1. Y Björk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Smith Knutsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Ankarberg-Lindgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A-K Broman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L Björkman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Magnusson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K Bergmark
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P-O Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Brune
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Brune.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Björk, Y., Smith Knutsson, E., Ankarberg-Lindgren, C. et al. Androgens in women after allogeneic hematopoietic cell transplantation: impact of chronic GvHD and glucocorticoid therapy. Bone Marrow Transplant 52, 431–437 (2017). https://doi.org/10.1038/bmt.2016.268

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.268

This article is cited by

Search

Advanced search

Quick links