leuprolide and Lupus-Erythematosus--Systemic

Administration of cyclophosphamide (CYC), an alkylating agent used to treat malignancies and severe rheumatic diseases, creates a risk of ovarian insufficiency that is related to the intensity and duration of therapy and the age of the patient. To preserve reproductive capacity in the appropriate clinical setting, oocyte, embryo, and/or ovarian tissue cryopreservation are recommended. Medical protection with depot gonadotropin-releasing hormone agonists (GNRHa) has emerged as a potential means to preserve both fertility and ovarian function through the suppression of ovarian activity during treatment with alkylators. We review the trials of GNRHa for ovarian protection in both cancer and rheumatic disease patients. Trials in cancer patients receiving CYC alone, or in combination with other gonadotoxic agents that have employed several different GNRHa have yielded mixed results. Trials in lupus patients receiving lower doses of CYC alone utilizing depot leuprolide acetate have tended to show favorable results.

Topics: Alkylating Agents; Cyclophosphamide; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Immunosuppressive Agents; Leuprolide; Lupus Erythematosus, Systemic; Primary Ovarian Insufficiency

A number of drugs have recently been implicated in a syndrome that resembles systemic lupus erythematosus. One of the difficulties in many of these patients is that the signs, symptoms and serological abnormalities reported in these patients may be a natural consequence of the primary diseases rather than the incriminated drug. A second problem with the studies is a lack of uniform reporting of the techniques used to detect autoantibodies. For example, a patient that has a highly positive ANA with a homogeneous pattern of staining or a positive LE cell test usually has antibodies directed against chromatin components (DNA, histones, high mobility group (HMG) proteins). The discrepancies in clinical criteria and the serological techniques in many of these reports, emphasize the importance of using guidelines for the diagnosis of drug-induced or drug-related lupus. In the future, it appears that the increased use of biological response modifiers such as interferon-alpha and other cytokines may prompt more reports of lupus syndromes associated with their use.

Topics: Deferiprone; Humans; Interferon-alpha; Interleukin-2; Leuprolide; Lupus Erythematosus, Systemic; Penicillamine; Pyridones; Sulfasalazine; Valproic Acid

Cyclophosphamide (CYC) therapy for systemic lupus erythematosus (SLE), a disease predominantly affecting women of childbearing age, causes an unacceptably high incidence of irreversible premature ovarian failure (POF). This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a), for protection against POF during CYC therapy.. Young women with severe SLE treated in a standardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH-a (depot leuprolide acetate; a 3.75-mg monthly injection during the standard CYC regimen). Patients treated with GnRH-a were compared with controls individually matched by age (+/-5 years) and by cumulative CYC dose (+/-5 gm). Reproductive status was determined after a minimum followup of 3 years after CYC therapy. The primary outcome was time to POF. Paired summary statistical analyses, Kaplan-Meier survival estimates, and Cox regression analyses were performed to assess differences in outcome between groups.. POF developed in 1 of 20 women treated with GnRH-a (5%) compared with 6 of 20 controls (30%) matched by age and cumulative CYC dose (matched odds ratio 0.09, P < 0.05). Kaplan-Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH-a-treated group (P = 0.04).. Treatment with GnRH-a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE.

Topics: Adult; Cyclophosphamide; Data Interpretation, Statistical; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Immunosuppressive Agents; Leuprolide; Lupus Erythematosus, Systemic; Ovary; Primary Ovarian Insufficiency; Survival Analysis; Treatment Outcome

To determine the effect of leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a) on ovarian function preservation in systemic lupus erythematosus (SLE) patients treated with cyclophosphamide (CYC) in clinical practice.. We enrolled 30 premenopausal female SLE patients who fulfilled the 1997 American College of Rheumatology revised criteria and were treated with intravenous CYC (IVCY) in 2008-2017. We used Kaplan-Meier survival estimates to compare the GnRH-a-treated patients and those not treated with GnRH-a as controls. We performed Cox regression analyses to identify factors associated with premature ovarian failure (POF), incidences of cardiovascular events, strokes and osteoporosis after IVCY therapy.. After a mean follow-up of 41 months, POF developed in one of the 16 GnRH-a-treated patients (6%) versus seven of the 14 controls (50%). Significantly improved cumulative ovarian protection over time was observed in the GnRH-a-treated group (P = 0.030). The hazard model analysis showed that treatment with GnRH-a during IVCY therapy is an independent factor associated with POF after IVCY therapy (adjusted hazards ratio = 0.12, 95% CI 0.01-0.67, P = 0.013) but not incidences of cardiovascular events, strokes or osteoporosis.. The combined use of GnRH-a with IVCY therapy was associated with a significant reduction of POF among premenopausal women with SLE, suggesting that the addition of GnRH-a can be a strategy to prevent POF among premenopausal women with SLE after IVCY therapy.

Topics: Administration, Intravenous; Adult; Cardiovascular Diseases; Case-Control Studies; Cyclophosphamide; Female; Fertility Agents, Female; Fertility Preservation; Humans; Immunosuppressive Agents; Incidence; Infertility, Female; Kaplan-Meier Estimate; Leuprolide; Lupus Erythematosus, Systemic; Multivariate Analysis; Osteoporosis; Ovary; Premenopause; Primary Ovarian Insufficiency; Proportional Hazards Models; Stroke; Time Factors; Treatment Outcome; Young Adult

To assess fertility counseling and preservation practices among children, adolescents, and young adults with rheumatic diseases undergoing cyclophosphamide (CTX) treatment.. Retrospective chart review (2006-2016).. Academic pediatric center.. Male and female patients with systemic lupus erythematosus, Wegener's granulomatosis/granulomatosis with polyangiitis, or other vaculitides, receiving CTX treatment.. None.. Documentation of fertility counseling and fertility preservation.. A total of 58 subjects met the inclusion criteria; 5 were excluded due to incomplete records, thus N = 53. Of these 75% were female (N = 40). Median age was 14 years at diagnosis and 15 years at first CTX treatment. A total of 51% of subjects (69% of males and 45% of females) had no documentation about potential fertility loss before CTX treatment. Among females where fertility counseling was documented, the only fertility preservation option discussed was leuprolide acetate (LA), which was pursued in all of these cases. Of 13 males (77% postpubertal), 3 were offered sperm banking, of whom 2 declined and the other attempted after treatment began and was azoospermic. Of 53 patients, 1 was referred to a fertility specialist. Mean cumulative CTX dose was 9.2 g in males and 8 g in females.. Based on these findings, increasing awareness about infertility risk, fertility preservation options, and referral to fertility specialists is needed among pediatric rheumatologists. Prospective studies are needed to assess fertility outcomes in this patient population (including effectiveness of LA with regard to pregnancy rates [PRs]), as well as barriers/facilitators to fertility counseling and fertility preservation.

Topics: Academic Medical Centers; Adolescent; Child; Child, Preschool; Counseling; Cyclophosphamide; Female; Fertility; Fertility Agents, Female; Fertility Preservation; Granulomatosis with Polyangiitis; Health Knowledge, Attitudes, Practice; Humans; Immunosuppressive Agents; Infertility, Female; Infertility, Male; Leuprolide; Lupus Erythematosus, Systemic; Male; Patient Acceptance of Health Care; Patient Education as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Semen Preservation; Young Adult

We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure.. Forty-eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed.. AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean ± SD: 0.18 ± 0.20 group I vs 1.33 ± 1.59 group III; p = 0.015), and versus group II (mean ± SD: 0.86 ± 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001).. Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury.

Topics: Adult; Anti-Mullerian Hormone; Biomarkers; Cohort Studies; Cyclophosphamide; Delayed-Action Preparations; Female; Fertility Agents, Female; Fertility Preservation; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Immunosuppressive Agents; Infertility, Female; Leuprolide; Lupus Erythematosus, Systemic; Ovary; Premenopause; Protective Agents; Retrospective Studies