Cyclophosphamide-Induced Ovarian Failure

Warne, Garry L.; Fairley, Kenneth F.; Hobbs, J. B.; Martin, F. I. R.

doi:10.1056/nejm197311292892202

Cited by 385 publications

(118 citation statements)

References 11 publications

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“…Although the toxic effects of cyclophosphamide on ovarian function have been observed since the 1960s in patients with rheumatoid arthritis using oral cyclophosphamide (24), many issues pertaining to gonadal insufficiency in patients with SLE remain unexplained to this day. There are very few articles in the medical literature that deal with these issues (3)(4)(5)(6)(7)(8)(12)(13)(14)(25)(26)(27), and the majority focus on the incidence of ovarian failure after cyclophosphamide use.…”

Section: Discussionmentioning

confidence: 99%

“…Gonadal toxicity should be of great concern in premenopausal women who take cyclophosphamide. The frequency of ovarian insufficiency in SLE patients treated with this drug ranges from 11 to 59% in different studies and depends on the dose used, the age of the patient and methodological differences (4)(5)(6)(7)(8)(12)(13)(14). Since estrogens have biological effects which protect the cardiovascular system, as well as the skeletal system from bone loss, estrogen deficiency is linked with a greater risk for cardiovascular disease (15) and osteoporosis (16), thus contributing to higher morbidity and mortality among patients diagnosed with lupus.…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for ovarian failure in patients with systemic lupus erythematosus

Medeiros

Silveira

Menezes

et al. 2001

Braz J Med Biol Res

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The aim of the present study was to identify the risk factors for ovarian failure in patients with systemic lupus erythematosus. Seventy-one women aged 17 to 45 years with systemic lupus erythematosus were studied. Patients were interviewed and their medical records reviewed. Demographic characteristics, clinical and serologic profiles, and menstrual and obstetric histories were recorded. Disease activity was measured by the systemic lupus erythematosus disease activity index. Serum FSH, LH, estradiol, progesterone, TSH, prolactin, and antimicrosomal and antithyroglobulin antibodies were measured. Patients who developed ovarian failure were compared to those who did not. Ovarian failure occurred in 11 patients (15.5%) and nine had premature menopause (11.3%). Cyclophosphamide administration and older patient age were found to be associated with ovarian failure. The cumulative cyclophosphamide dose was significantly higher in patients with ovarian failure than in those without this condition (18.9 vs 9.1 g; P = 0.04). The relative risk for ovarian failure in patients with cumulative cyclophosphamide dose higher than 10 g was 3.2. TSH levels were high in 100% of patients with ovarian failure who had received pulse cyclophosphamide. Ovarian failure, and premature menopause in particular, is common in patients with systemic lupus erythematosus, with the most important risk factors being cyclophosphamide dose and age. Thyroid problems may be another risk factor for ovarian failure in patients with lupus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risk factors for ovarian failure in patients with systemic lupus erythematosus

Medeiros

Silveira

Menezes

et al. 2001

Braz J Med Biol Res

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“…Ovarian biopsies performed in patients undergoing chemoradiotherapy showed ovarian damage accompanied by fibrosis, with no evidence of follicular maturation. [14][15][16][17] Pregnancies do occur among patients who have undergone HSCT as children; however, they are rare. The aims of this study were to identify pregnancies and their outcomes as well as to determine fertility status and possible risk factors for infertility in former patients treated at seven European HSCT centres.…”

Section: Introductionmentioning

confidence: 99%

Fertility after allogeneic haematopoietic stem cell transplantation in childhood and adolescence

Borgmann‐Staudt

Rendtorff

Reinmuth

et al. 2011

Bone Marrow Transplant

158

123

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Infertility is a major late effect in patients receiving haematopoietic stem cell transplantation (HSCT). The aim of this study was to determine the proportion of patients having fertility impairment after allogeneic HSCT in childhood/adolescence and to identify the potential risk factors. Treatment and fertility data of paediatric patients with malignant and non-malignant diseases treated with allogeneic HSCT between 2000 and 2005 were collected from seven European centres. Data were obtained for 138 female and 206 male patients after a median follow-up of 6 years (range 3-12). The patients' median age was 13 years (range 4-28) at the time of years at the time of the enquiry. Seven children were born to the overall group, all at term and healthy. Fertility impairment was suspected in 69% males and 83% females. Start of treatment at age X13 years was a risk factor in females (odds ratio (OR) 4.7; 95% confidence interval (CI), 1.5 to 14.9), whereas pre-pubertal therapy was a risk factor in males (OR 0.4; 95% CI, 0.2 to 0.8). The major treatment-related risk factors were BU in females (OR 47.4; 95% CI, 5.4 to 418.1) and TBI in males (OR 7.7; 95% CI, 2.3 to 25.4). In light of the significant proportion of HSCT patients reviewed with impaired fertility, fertility conservation procedures should be considered for all patients undergoing HSCT, particularly those receiving TBI or BU-based preparative regimens.

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“…Chemotherapy-related amenorrhea is generally linked to the patient's age as well as treatment protocol (types of chemotherapeutic agents used, doses and schedules) Bonadonna et al As previously mentioned, the incidence of ovarian dysfunction is related to patient age, the specific agents used and the total dose administered, especially the dose of alkyaling agents such as cyclophosphamide. Amenorrhea rates following combination chemotherapy consisting of CMF regimens range from 21% to 71% in women aged 40 years and younger, and from 40% to 100% in older ones Bonadonna et al (2005); Goldhirsch et al (1990); Padmanabhan et al (1986); Warne et al (1973). In the interpretation of the data with CMF regimens, many difficulties exist due to a lack of homogeneity of CMF regimens: variations in the doses and type of administration of cyclophosphamide (oral vs. intravenous) and variations in the total number of courses: 3 to 12 courses.…”

Section: Defining Chemotherapy-related Amenorrheamentioning

confidence: 99%