Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study
Abstract Background Ovarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease a...
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2020-08-01
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Series: | Arthritis Research & Therapy |
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Online Access: | http://link.springer.com/article/10.1186/s13075-020-02292-y |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shefali Khanna Sharma Siddharth Jain Pooja Bahl Pragna Potturi Manish Rathi Shankar Naidu Naresh Sachdeva Varun Dhir Sanjay Jain |
spellingShingle |
Shefali Khanna Sharma Siddharth Jain Pooja Bahl Pragna Potturi Manish Rathi Shankar Naidu Naresh Sachdeva Varun Dhir Sanjay Jain Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study Arthritis Research & Therapy Cyclophosphamide Gonadotoxicity Systemic lupus erythematosus Mycophenolate mofetil Ovarian dysfunction |
author_facet |
Shefali Khanna Sharma Siddharth Jain Pooja Bahl Pragna Potturi Manish Rathi Shankar Naidu Naresh Sachdeva Varun Dhir Sanjay Jain |
author_sort |
Shefali Khanna Sharma |
title |
Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study |
title_short |
Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study |
title_full |
Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study |
title_fullStr |
Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study |
title_full_unstemmed |
Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study |
title_sort |
ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified nih regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2020-08-01 |
description |
Abstract Background Ovarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease activity, by itself, is also believed to affect ovarian function negatively. Methods This single-centre prospective cohort study recruited 50 female patients of severe lupus aged 18–40 years. Twenty-five patients each received induction with either monthly intravenous CYC (0.5–0.75 g/m2) for 6–9 months or daily oral mycophenolate mofetil (MMF). Details of menstrual irregularities; serum levels of FSH, LH, estradiol, AMH, and inhibin B; and sonographic assessment of ovarian volume and antral follicular count were done at baseline and 6 months after treatment. Amenorrhoeic patients were re-evaluated at 1 year. Results Mean (SD) age of subjects in the CYC and MMF groups was 31.4 (6.3) and 28.4 (4.4) years, respectively. Mean (SD) SLEDAI at the initiation of therapy was 7.2 (2.5) in the CYC group and 5.8 (3.4) in the MMF group. The mean cumulative dose of CYC used was 4.6 (1.8) g. Three patients in the CYC group (versus none in MMF) had amenorrhoea at 6 months—two of these regained menses within 6 months, while only one (4%) developed sustained amenorrhoea (lasting more than 12 months) at 41 years of age, likely menopause. Serum FSH levels increased (p = 0.03), while AMH (p = 0.002) and inhibin B (p < 0.001) levels decreased significantly with 6 months of CYC therapy. Ovarian volume also reduced significantly (p = 0.005) with 6 months of CYC therapy, while antral follicular count reduced numerically (p = 0.32). Levels of AMH, inhibin-B, estradiol, ovarian volume, and antral follicular count after 6 months therapy were significantly lesser in the CYC group compared to the MMF group, despite being similar before the start of therapy. Conclusions Ovarian dysfunction with monthly intravenous CYC (modified NIH regimen) was predominantly subclinical, with a negative effect on ovarian reserve. No premature ovarian failure was noted at 1 year. No ovarian dysfunction occurred in the MMF group, despite having patients with severe background lupus. Use of intravenous CYC for induction may thus not be restricted in young lupus females with incomplete families for fear of gonadotoxicity, especially in life- or organ-threatening situations, where the benefits outweigh this subclinical risk. |
topic |
Cyclophosphamide Gonadotoxicity Systemic lupus erythematosus Mycophenolate mofetil Ovarian dysfunction |
url |
http://link.springer.com/article/10.1186/s13075-020-02292-y |
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doaj-94ccea1358e943e1be0a7efa0d7d099d2020-11-25T03:42:13ZengBMCArthritis Research & Therapy1478-63622020-08-012211810.1186/s13075-020-02292-yOvarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort studyShefali Khanna Sharma0Siddharth Jain1Pooja Bahl2Pragna Potturi3Manish Rathi4Shankar Naidu5Naresh Sachdeva6Varun Dhir7Sanjay Jain8Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and ResearchClinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and ResearchDepartment of Obstetrics and Gynaecology, Postgraduate Institute of Medical Education and ResearchClinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and ResearchDepartment of Nephrology, Postgraduate Institute of Medical Education and ResearchClinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and ResearchDepartment of Endocrinology, Postgraduate Institute of Medical Education and ResearchClinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and ResearchClinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and ResearchAbstract Background Ovarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease activity, by itself, is also believed to affect ovarian function negatively. Methods This single-centre prospective cohort study recruited 50 female patients of severe lupus aged 18–40 years. Twenty-five patients each received induction with either monthly intravenous CYC (0.5–0.75 g/m2) for 6–9 months or daily oral mycophenolate mofetil (MMF). Details of menstrual irregularities; serum levels of FSH, LH, estradiol, AMH, and inhibin B; and sonographic assessment of ovarian volume and antral follicular count were done at baseline and 6 months after treatment. Amenorrhoeic patients were re-evaluated at 1 year. Results Mean (SD) age of subjects in the CYC and MMF groups was 31.4 (6.3) and 28.4 (4.4) years, respectively. Mean (SD) SLEDAI at the initiation of therapy was 7.2 (2.5) in the CYC group and 5.8 (3.4) in the MMF group. The mean cumulative dose of CYC used was 4.6 (1.8) g. Three patients in the CYC group (versus none in MMF) had amenorrhoea at 6 months—two of these regained menses within 6 months, while only one (4%) developed sustained amenorrhoea (lasting more than 12 months) at 41 years of age, likely menopause. Serum FSH levels increased (p = 0.03), while AMH (p = 0.002) and inhibin B (p < 0.001) levels decreased significantly with 6 months of CYC therapy. Ovarian volume also reduced significantly (p = 0.005) with 6 months of CYC therapy, while antral follicular count reduced numerically (p = 0.32). Levels of AMH, inhibin-B, estradiol, ovarian volume, and antral follicular count after 6 months therapy were significantly lesser in the CYC group compared to the MMF group, despite being similar before the start of therapy. Conclusions Ovarian dysfunction with monthly intravenous CYC (modified NIH regimen) was predominantly subclinical, with a negative effect on ovarian reserve. No premature ovarian failure was noted at 1 year. No ovarian dysfunction occurred in the MMF group, despite having patients with severe background lupus. Use of intravenous CYC for induction may thus not be restricted in young lupus females with incomplete families for fear of gonadotoxicity, especially in life- or organ-threatening situations, where the benefits outweigh this subclinical risk.http://link.springer.com/article/10.1186/s13075-020-02292-yCyclophosphamideGonadotoxicitySystemic lupus erythematosusMycophenolate mofetilOvarian dysfunction |