Gonadal function and bone marrow transplantation (original) (raw)
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BACKGROUND: Ovarian failure is a frequent complication occurring after haematopoietic stem cell transplantion (SCT), which is generally ascribed to radiation treatment and antiblastic alkylating agents. METHODS: Ovarian morphology and function were studied in reproductive age women 12±24 months after allogeneic SCT (n = 23) received from an HLA identical sibling, or autologous SCT (n = 22). Thirteen allo-transplanted women were suffering from chronic graft-versus-host disease (cGVHD). RESULTS: Menstrual cycles recovered in two and four women in the allo-and auto-SCT groups respectively, being associated with younger age and longer period elapsed from transplant. There was no difference in previous use of alkylating agents between allo-and auto-transplantation, while corticosteroid treatment was longer and more recent in the allo-SCT group. Signi®cantly higher gonadotrophin levels and lower estradiol were seen in the combined group of patients than in controls. In allo-transplanted women, androgens were also signi®cantly lower than in controls. Ovarian and uterine volumes were lower in patients than in controls, and in the allo-than in the auto-transplanted women. Within the allo-SCT group, endocrine function and ovarian and uterine volumes were signi®cantly lower in the patients suffering from cGVHD. CONCLUSIONS: Ovarian failure in SCT recipients is likely to be caused principally by myelo-ablative treatments, but the condition of gonadal and androgen insuf®ciency can be worsened by an altered immunomodulation in allogeneic setting.
Fertility and Sterility, 2011
Objective: To evaluate which factors determine premature ovarian failure after bone marrow transplantation (BMT) during childhood and adolescence. Design: Cross-sectional study. Setting: Academic teaching hospital. Patient(s): Thirty-five women with previous allogeneic (n ¼ 19) or autologous (n ¼ 16) BMT for benign (n ¼ 12) or malignant disease (n ¼ 23). Mean age at BMT was 9.8 AE 5.2 years. Eighteen patients had received total body irradiation (TBI). Twenty-three (66%) were premenarchal at the time of BMT. Intervention(s): Evaluation of ovarian function. Main Outcome Measure(s): Retrospective analysis of gynecologic history and hormone measurements (FSH, E 2 , and antim€ ullerian hormone [AMH]) in relation to initial pathology, treatment protocols, age, and menarchal status at the time of BMT and time elapsed since BMT. Result(s): Clinical evidence of persistent ovarian function after BMT was found in 46% of patients (16/35), but low AMH concentrations (<1.2 mg/L) were observed in 85% of patients, including a large subset (2/3) of clinically eugonadal subjects. Age %10 years at the time of BMT and absence of TBI were significantly and independently associated with higher rates of clinically proven persistent ovarian function at the time of evaluation. Conclusion(s): After BMT, ovarian function is impaired in the majority of women, even without clinical signs of premature ovarian failure. This impairment is mostly related to older age at the time of treatment and conditioning treatment with TBI. (Fertil Steril Ò 2011;96:126-133.
Gonadal Function of Young Patients with Beta-Thalassemia Following Bone Marrow Transplantation
Journal of Pediatric Endocrinology and Metabolism, 2005
Bone marrow transplantation (BMT) can induce short-and long-term impairment of gonadal function. Patients with beta-thalassemia represent a special group, as their primary diagnosis and its treatment modalities are responsible for gonadal dysfunction. To address the effect of BMT on puberty and gonadal function, we investigated 25 patients (12 males) with thalassemia who received allogenic BMT during childhood or adolescence and at the posttransplant evaluation were at an age that the pubertal process should have started. Pubertal stage by Tanner of breast and pubic hair, as well as testicular volume were assessed pre-BMT once and post-BMT at least twice. Menstrual history was recorded. FSH, LH, testosterone and estradiol levels were also determined. The impact of BMT appears to be different in the two sexes. Males seem to have higher tolerance, as all males who were pubertal at the time of BMT had normal testosterone, and all but one normal gonadotropin levels. From those who were prepubertal at BMT, 62% proceeded to normal pubertal development. Post-menarcheal females seem to be an extremely sensitive group to the deleterious effect of the transplantation process, as 100% of the post-menarcheal females exhibited amenorrhea and elevated gonado
Gonadal function after bone marrow transplantation for acute leukemia during childhood
The Journal of Pediatrics, 1997
To examine the impact of bone marrow transplantation (BMT), using high-dose chemotherapy and hyperfractionated total body irradiation, on gonadal function in survivors of acute leukemia treated during childhood. Study design: We conducted a retrospective study of 33 subjects (I 7 boys) who underwent a BMT for acute leukemia (acute lymphoblastic leukemia, n = 20; acute myelogenous leukemia, n = 13) at a single institution. All patients were prepubertal at the time of BMT (median age, 7. I years [3.7 to 11.6 years]); at the time of their last examination the boys were a median of 14 years (10.4 to 17.1 years) of age and the girls were a median of 16.9 years (9.5 to 21.9 years) of age. Results: Of 17 boys, 14 (82%) entered puberty spontaneously and 13 demonstrated age-appropriate plasma concentrations of testosterone. Two boys (aged 10.5 and 11 years) remain clinically and hormonally prepubertal, and one boy has overt Leydig cell failure requiring androgen replacement therapy. Thirty-six percent of pubertal boys have elevated plasma concentrations of luteinizing hormone and 64% have raised levels of follicle-stimulating hormone. Boys with increased levels of luteinizing hormone were significantly younger at BMT (5.4-0.8 vs 7.8 _ 0.8 years; p= 0.024). Of 16 girls, 9 (56%) had spontaneous puberty with onset of menarche at a median age of 13 years (9.5 to 15.8 years). Though six (67%) of these nine girls have had increased, plasma concentrations of luteinizing and follicle-stimulating hormones, normalization has occurred in two during a period of 4 to 7 years. The remaining seven subjects required hormone replacement because of clinical and biochemical evidence of ovarian failure. One of these subjects has recovered ovarian function after 5~ years. Female patients with ovarian failure were significantly older at BMT compared with female patients with spontaneous puberty/menarche (8.6-23 years vs 6.1 ~ 1.8; p = 0.03). Conclusion: Our results indicate that most prepubertal boys undergoing BMT with chemotherapy and hyperfractionated total body irradiation can expect to enter and progress normally through puberty. For prepubertal girls treated with these regimens, at least 50% retain adequate ovarian function to enter puberty and menstruate regularly.
The Journal of Clinical Endocrinology & Metabolism, 2011
Context: In young women, some treatments for cancer or other conditions (such as sickle cell anemia) may give rise to primary ovarian insufficiency. Ovarian transplantation is one of the available options for fertility preservation, with highly variable pregnancy rates. Objective: The objective of the study was to investigate markers of ovarian reserve and ovarian function in women up to 7 yr after orthotopic ovarian transplantation. Secondary objectives were to assess the relationship between markers of ovarian reserve and pregnancy rate along with the duration of ovarian function. Design: This was a prospective cohort study in 10 women, with a mean follow-up of 2.5 yr. Setting: The study was conducted at a university hospital in Brussels, Belgium. Patients: Patients included 10 women who were about to receive or had previously received gonadotoxic treatment. In seven women cryopreservation of ovarian tissue was performed before starting treatment. Subsequently autografts were orth...
Biology of Blood and Marrow Transplantation
Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre-and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P < .001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.
Biology of Blood and Marrow Transplantation, 2019
Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre-and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P < .001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.
Osteoporosis International, 2001
Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48 Ô 13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2-L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score 5-2.5 SD and the mean BMD was 0.806 Ô 0.11 g/cm 2 (range 0.470-1.045 g/cm 2 ). The BMD was lower 3 months after OLTx and significantly higher 12 and 24 months after OLTx. A significant increase in serum BGP was observed at 6, 12 (p50.05) and 24 months (p50.005) after OLTx. The mean serum PTH level was 26.6 Ô 3.1 pg/ml at baseline and increased significantly at 12 and 24 months (to 49.4 Ô 9.9 and 61.2 Ô 10.1 pg/ml, respectively; p50.05). 25OHD serum levels were low at baseline and returned to the normal range after 12 and 24 months (baseline, 8.73 Ô 1.54 ng/ ml; 12 months, 16.4 Ô 2.6 ng/ml; 24 months, 17.67 Ô 3.1 ng/ml; p50.05). FT was significantly lower at baseline than in a group of 10 healthy controls (5.09 Ô 10.99, vs 10.3 Ô 1.1 pg/ml; p50.0001). After OLTx a significant increase in FT was recorded at 6, 12 (p50.05) and 24 months (p50.005). FT was not correlated with BMD, however. After OLTx an increase in FSH and LH was observed (but failed to reach statistical significance) at 3 and 6 months, followed by a slight reduction at 12 and 24 months. Thus a high proportion of men with end-stage liver disease do have osteoporosis. After OLTx, an early recovery of gonad function is observed, followed by an increase in bone mass, which occurs from the sixth month onward.
Ovarian Transplant: A New Frontier
Transplantation Proceedings, 2005
Two cases of orthotopic ovarian transplantations were performed on patients diagnosed to have Turner's syndrome (ovarian dysgenesis) with primary amenorrhea, short stature, and absent secondary sexual characters. Chromosomal analysis showed 45XO pattern. Both transplants were living related from a sister and from a mother. In both the cases the donor and the recipient were immunologically matched by blood group, histocompatibility antigens (HLA), and lymphocyte cross-match done twice. The donor ovaries were dissected extraperitoneally to have long vascular pedicles. In the first case the donor ovarian vein was sutured end-to-side to external iliac vein and the ovarian artery was sutured to the inferior epigastric artery end-to-end using an operative microscope. The ovary was placed in the orthotopic position transperitoneally. Follow-up for 2.5 years has shown regular menstruations, documented ovulations, rise in hormonal levels, and development of secondary sexual characters. In the second case there was no large vein available for anastomosis so that an avascular orthotopic transplantation was performed. The ovarian cortex was dissected in a fan-shaped manner of 0.5-cm strips. Two grafts sutured onto surgicel were placed orthotopically in the ovarian fossa and the remaining ones were placed into the broad ligament. One month follow-up shows good take-up and follicular development on USG, power-angio, and MRI. Hormonal rise has indicated functioning graft. Immunosuppression was achieved in both cases using cyclosporine (4 mg/kg) and prednisolone (2 mg/kg).
Gonadal Function and Immunosuppressive Therapy After Renal Transplantation
Transplantation Proceedings, 2005
End-stage renal disease is associated with disorders in hypothalamic-pituitary-gonadal function. Immunosuppressive therapies may influence the restoration of normal levels of gonadal hormones after renal transplantation. The aim of the present study was to evaluate the hormonal status of successful renal transplant recipients who were treated with different immunosuppressive agents. Methods. Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in 59 male renal transplant recipients with stable graft function with serum creatinine Ͻ2.5 mg/dL. Patients were treated with three different immunosuppressive regimens: group I, calcineurin inhibitors (CI; n ϭ 15), group II, sirolimus without calcineurin inhibitors (SRL; n ϭ 15), group III, sirolimus in combination with calcineurin inhibitors (SRL ϩ CI; n ϭ 29). Results. Testosterone was significantly lower in group II versus group I (3.12 Ϯ 1.23 versus 4.39 Ϯ 1.53 ng/mL; P Ͻ .0197). Group III had higher testosterone values than group II, but lower than group I. FSH and LH were also higher in the SRL group, but the differences were not statistically significant, perhaps because of the small number of patients. No relationship was found between testosterone blood levels and age, posttransplant follow-up, renal function, time on dialysis, body mass index, steroid use, or posttransplant diabetes. Conclusion. Sirolimus seems to impair the improvement of gonadal function after renal transplantation. Further prospective studies are needed to confirm these data before patients are advised of this potential side effect.