Effects of Chemotherapy-Induced Testicular Damage on Inhibin, Gonadotropin, and Testosterone Secretion: A Prospective Longitudinal Study

Wallace, Euan; Groome, Nigel P.; Riley, Simon; Parker, A. C.; Wu, Frederick C. W.

doi:10.1210/jcem.82.9.4238

Cited by 88 publications

(40 citation statements)

References 41 publications

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“…Inhibin B levels are reduced in patients with spermatogenic failure and show a reciprocal relationship with FSH during chemotherapy-induced spermatogenic damage. 7 In our study we observed a significant correlation of inhibin B levels with sperm counts. However, while all five patients with very low inhibin B levels were azoospermic, inhibin B levels did not reliably distinguish the non-azoospermic patients from the other four azoospermic patients.…”

Section: Discussionsupporting

confidence: 59%

Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg)

Grigg

McLachlan

Zajac

et al. 2000

Bone Marrow Transplant

122

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Summary:There are few published data on the recovery of fertility after 'little' Bu-Cy (busulfan 16 mg/kg, cyclophosphamide 120 mg/kg) conditioning for BMT. To address this, we identified 19 females aged less than 40 years at transplant and 47 males from a single centre who were alive a minimum of 2 years after BMT with little Bu-Cy as conditioning and who were evaluable for testing. FSH, LH, testosterone and inhibin B levels were measured in males. Twenty-six also had semen analysis, a median of 5 years post transplant; 21 had detectable sperm, with 11 having counts Ͼ20 × 10 6 /ml. There was an association between prolonged chronic graft-versus-host disease and low sperm counts. FSH and inhibin B levels correlated with sperm counts but not to the extent that they could reliably predict counts in individual patients. An additional six of seven males attempting to father children did so, a median of 3.2 years post transplant. Low testosterone levels were noted in 12% of males, most of whom had symptoms consistent with androgen deficiency. FSH, LH and oestradiol levels in the absence of hormone replacement therapy were measured in females; all remained amenorrheic with endocrine evidence of ovarian failure. These results have implications for fertility counselling and hormone replacement therapy both pre-and post BMT. Bone Marrow Transplantation (2000) 26, 1089-1095. Keywords: busulfan; cyclophosphamide; marrow transplantation; fertility; testosterone Myeloablative conditioning regimens comprising high dose combination alkylating agents have been conventionally considered to cause permanent infertility in the vast majority of adult patients of either sex undergoing allogeneic or autologous marrow or peripheral blood stem cell transplantation. The most widely used non-total body irradiation (TBI) regimen prior to allografting is busulfancyclophosphamide (Bu-Cy). To our knowledge, the only substantial peer-reviewed publication of the effects of BuCy on fertility has been published by the Seattle group in

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Section: Discussionsupporting

confidence: 59%

Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg)

Grigg

McLachlan

Zajac

et al. 2000

Bone Marrow Transplant

122

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“…19 We found a negative correlation between inhibin B and FSH concentrations. Wallace et al 20 found that inhibin B fell 1 month after chemotherapy for hematological malignancies, and that FSH increased within the first month. Both reached plateau values at 4 months, did not change thereafter until 12 months, and were significantly and negatively correlated.…”

Section: Discussionmentioning

confidence: 99%

Factors affecting gonadal function after bone marrow transplantation during childhood

Couto-Silva

Trivin

Thibaud

et al. 2001

Bone Marrow Transplant

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Summary:Conditioning for bone marrow transplantation (BMT) may alter viability of germ cells and production of gonadal hormones. We analyzed the risk factors for gonadal failure after 12 Gy total body irradiation (TBI) given as six fractions (n = 31, group 1), 10 Gy (one dose) TBI (n = 20, group 2), 6 Gy (one dose) total lymphoid irradiation (TLI, n = 17, group 3) and chemotherapy alone (n = 7, group 4), given at 7.7 ± 0.4 (0.6-13.6) years. Among the 34 girls, seven (20.6%) had normal ovarian function with regular spontaneous menstruation and normal plasma follicle-stimulating (FSH) and luteinizing (LH) hormones, five (14.7%) had partial ovarian failure with regular menstruation but increased FSH and/or LH, and 22 (64.7%) had complete ovarian failure. The 24 girls with chronological and bone ages Ͼ13 years included similar percentages, with increased FSH or LH in all four groups. There was a positive correlation between age at BMT and FSH (r = 0.54, P Ͻ 0.01), but not with LH, and between FSH and LH (r = 0.8, P = 0.0003). Plasma FSH concentrations had returned to normal spontaneously in six cases, and those of LH in two cases. Among the 41 boys, 16 (39%) had normal testicular function and 25 (61%) had tubular failure and increased FSH. Of these, 10 also had Leydig cell failure (three complete and seven partial). The 18 boys with chronological and bone ages Ͼ15 years included similar percentages with increased FSH or LH in groups 1 to 3, and testicular volume was significantly lower in group 2 than in group 3 (P = 0.008). There was no correlation between age at BMT and FSH, LH or testosterone, but there was a negative correlation between FSH and inhibin B (rho = −0.87, P Ͻ 0.003). We conclude that girls are more likely to suffer ovarian failure the older they are at BMT, and that early ovarian recovery is possible. Keywords: bone marrow transplantation; fertility; inhibin; irradiation; ovary; testis Conditioning for bone marrow transplantation (BMT) may alter the production of gonadal hormones (estradiol and progesterone in girls, testosterone in boys) and the viability of germ cells. 1-3 Gonadal failure results in incomplete sexual development and growth at puberty, and sterility in adulthood. Gonadal hormones are required for the development of secondary sexual characteristics, and for the growth acceleration which normally occurs at puberty.The risk factors for gonadal failure in patients undergoing BMT are difficult to analyze because of the variety of conditioning regimens used, and the possibility of gonadal recovery. 4 This study analyzes the expression and frequency of gonadal failure in both sexes according to the conditioning protocol, and the significance of the age during childhood at which BMT is carried out. We also measured plasma inhibin B concentrations as an additional marker of tubular function in these young patients where semen analysis is not possible. PatientsThe gonadal function of 75 patients (34 girls and 41 boys) who received a BMT during childhood, and who were aged more than 10 years ...

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“…The importance of these alterations were accurately surmised as being detrimental to fertility, but the limitations of these studies prevented meaningful application in clinical practice (Hensley and Reichman, 1998). Prospective studies are limited and have been performed in women and men with haematological malignancy (Chatterjee et al, 1994;Wallace et al, 1997).…”

Section: P<001mentioning

confidence: 99%

Predictors of ovarian reserve in young women with breast cancer

et al. 2007

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Ovarian reserve can be diminished following treatment for breast cancer. This study evaluated biochemical and biophysical parameters of ovarian reserve in these patients. Biochemical and biophysical tests of ovarian reserve were performed simultaneously in young (age 22 -42 years), regularly menstruating women with breast cancer (n ¼ 22) and age-matched controls (n ¼ 24). All tests were performed before (baseline) and after transient ovarian stimulation in the early follicular phase. Patients were recruited both before and after completion of chemotherapy, with some patients being followed up prospectively. Serum samples were analysed for follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E 2 ), inhibins A and B, and antimullerian hormone (AMH). Biophysical (ultrasound) tests included ovarian volume, antral follicle count (AFC), ovarian stromal blood flow and uterine dimensions. Significant differences were revealed (when compared with the controls) for basal FSH (11.3271

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Effects of Chemotherapy-Induced Testicular Damage on Inhibin, Gonadotropin, and Testosterone Secretion: A Prospective Longitudinal Study

Cited by 88 publications

References 41 publications

Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg)

Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg)

Factors affecting gonadal function after bone marrow transplantation during childhood

Predictors of ovarian reserve in young women with breast cancer

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