mycophenolic-acid and Primary-Ovarian-Insufficiency

One of the side effects of cyclophosphamide is earlier menopause and primary ovarian insufficiency. This study was undertaken to investigate the onset of menopause and the incidence of primary ovarian insufficiency in women with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), especially after treatment with orally administered cyclophosphamide.. We retrospectively studied the onset of menopause and the influence of cyclophosphamide in women diagnosed as having AAV in our center between 1970 and 2012.. Ninety-four premenopausal women diagnosed as having AAV were included. Sixty-seven patients received cyclophosphamide, and 27 received other, mostly immunosuppressive, medication. Forty-six cyclophosphamide-treated women developed menopause, 22 of whom were considered to have primary ovarian insufficiency. None of the patients who were not treated with cyclophosphamide developed primary ovarian insufficiency. There was a significant association between a cumulative cyclophosphamide dose of >16.6 gm, versus a cumulative dose of <16.6 gm, and menopause (χ(2)  = 8.72, P = 0.003; odds ratio [OR] 2.60 [95% confidence interval 1.38-4.90]). In addition, there was a significant association between a cumulative cyclophosphamide dose of <16.6 gm, versus no cyclophosphamide exposure, and menopause (χ(2)  = 16.37, P < 0.001; OR 7.32 [95% confidence interval 2.79-19.20]). Both women who received cyclophosphamide and those who did not experienced involuntary childlessness.. Earlier menopause and primary ovarian insufficiency frequently develop after oral cyclophosphamide therapy in premenopausal women with AAV. Involuntary childlessness is common after the development of primary ovarian insufficiency, but it also occurs in women not treated with cyclophosphamide. These findings emphasize the importance of the use of drugs that are not toxic to gonadal function in women of childbearing age.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Case-Control Studies; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Incidence; Maintenance Chemotherapy; Menopause; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisolone; Primary Ovarian Insufficiency; Remission Induction; Retrospective Studies; Risk Factors; Rituximab; Young Adult

Kidney involvement is common in systemic lupus erythematosus, occurring in up to 60% of affected adults during the course of their disease. Diffuse proliferative lupus nephritis (World Health Organization class IV), the most ominous variant, has traditionally been treated with cyclophosphamide and glucocorticoids. With cyclophosphamide, women of childbearing potential must weigh the risks of sustained amenorrhea, infertility, increased susceptibility to infection, bone marrow suppression, hemorrhagic cystitis, and malignancy against the benefits of better disease control compared with glucocorticoids alone. Because of the host of adverse effects associated with cyclophosphamide, alternative approaches to the treatment of lupus nephritis are desirable. A 31-year-old woman developed class IV lupus nephritis in the postpartum period. Seeking to preserve fertility and avoid other known toxicities of cyclophosphamide, she chose to undergo therapy with mycophenolate mofetil. In the treatment of severe lupus nephritis, mycophenolate mofetil has emerged as an alternative to cyclophosphamide, offering a major advance in the therapy of lupus nephritis.

Topics: Adult; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Primary Ovarian Insufficiency