| 1. |
- Altmae, Signe, et al.
(författare)
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Variations in folate pathway genes are associated with unexplained female infertility
- 2010
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 94:1, s. 130-137
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility. Design: An association study. Setting: Hospital-based IVF unit and university-affiliated reproductive research laboratories. Patient(s): Seventy-one female patients with unexplained infertility. Intervention(s): Blood samples for polymorphism genotyping and homocysteine, vitamin B12, and folate measurements. Main Outcome Measure(s): Allele and genotype frequencies of the following polymorphisms: 5,10-methylenetetra-hydrofolate reductase (MTHFR) 677C/T, 1298A/C, and 1793G/A, folate receptor 1 (FOLR1) 1314G/A, 1816delC, 1841G/A, and 1928C/T, transcobalamin II (TCN2) 776C/G, cystathionase (CTH) 1208G/T and solute carrier family 19, member 1 (SLC19A1) 80G/A, and concentrations of plasma homocysteine, vitamin B12, and serum folate. Result(s): MTHFR genotypes 677CT and 1793GA, as well as 1793 allele A were significantly more frequent among controls than in patients. The common MTHFR wild-type haplotype (677, 1298, 1793) CAG was less prevalent, whereas the rare haplotype CCA was more frequent in the general population than among infertility patients. The frequency of SLC19A1 80G/A genotypes differed significantly between controls and patients and the A allele was more common in the general population than in infertile women. Plasma homocysteine concentrations were influenced by CTH 1208G/T polymorphism among infertile women. Conclusion(s): Polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. (Fertil Steril (R) 2010;94:130-7. (C) 2010 by American Society for Reproductive Medicine.)
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| 2. |
- Baumgart, Juliane, 1978-, et al.
(författare)
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Androgen levels during adjuvant endocrine therapy in postmenopausal breast cancer patients
- 2014
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Ingår i: Climacteric. - London, United Kingdom : Informa Healthcare. - 1369-7137 .- 1473-0804. ; 17:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate plasma steroid hormone levels in postmenopausal breast cancer patients with and without adjuvant endocrine therapy and in healthy postmenopausal women.Methods: Steroid hormone levels in postmenopausal breast cancer patients treated with aromatase inhibitors (n = 32) were compared with breast cancer patients treated with tamoxifen (n = 34), breast cancer patients without adjuvant endocrine therapy (n = 15), and healthy postmenopausal women (n = 56). Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone (DHEA), androstenedione, total testosterone, dihydrotestosterone, estrone and estradiol were measured using liquid chromatography-tandem mass spectrometry. Sex hormone binding globulin was measured by solid-phase chemiluminescent immunometric assays, and the free androgen index was calculated.Results: Aromatase inhibitor users did not differ in dihydrotestosterone, total testosterone, androstenedione, DHEA, or free androgen index levels from healthy controls or untreated breast cancer patients. The highest total testosterone levels were found in tamoxifen-treated women, who had significantly higher plasma concentrations than both women treated with aromatase inhibitors and breast cancer patients without adjuvant treatment. Concentrations of cortisol and cortisone were significantly greater in aromatase inhibitor users as well as tamoxifen users, in comparison with healthy controls and untreated breast cancer patients. Aromatase inhibitor users had lower estrone and estradiol plasma concentrations than all other groups.Conclusion: Adjuvant treatment with aromatase inhibitors or tamoxifen was associated with increased cortisol and cortisone plasma concentrations as well as decreased estradiol concentrations. Androgen levels were elevated in tamoxifen-treated women but not in aromatase inhibitor users.
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| 3. |
- Baumgart, Juliane, 1978-, et al.
(författare)
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Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer
- 2013
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Ingår i: Menopause. - : Lippincott Williams & Wilkins. - 1072-3714 .- 1530-0374. ; 20:2, s. 162-168
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The goal of this study was to investigate sexual function in postmenopausal breast cancer patients treated with aromatase inhibitors.Methods: A population-based, cross-sectional study was conducted among postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched controls with and without estrogen treatment. Sexual function was assessed with a standardized questionnaire.Results: In all, 42.4% of aromatase inhibitor-treated breast cancer patients were dissatisfied with their sex life in general, and 50.0% reported low sexual interest; this was significantly more common than in tamoxifen-treated patients and controls (P < 0.05). Aromatase inhibitorYtreated patients reported insufficient lubrication in 73.9% and dyspareunia in 56.5% of cases, which were significantly more common than in controls, irrespective of hormonal use (P < 0.05). Tamoxifen-treated patients reported significantly more dyspareunia (31.3%; P < 0.05) but resembled controls in all other concerns.Conclusions: Our findings suggest that sexual dysfunction in aromatase inhibitorYtreated women is a greatly underestimated problem.
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| 4. |
- Baumgart, Juliane, et al.
(författare)
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Urogenital disorders in women with adjuvant endocrine therapy after early breast cancer
- 2011
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 204:1, s. 26.e1-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the prevalence of urogenital symptoms and vaginal atrophy in postmenopausal breast cancer patients on adjuvant endocrine therapy. STUDY DESIGN: A population-based, cross-sectional study on postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched control subjects. Vaginal atrophy was assessed by gynecologic examination and atrophy-related symptoms by validated questionnaires. RESULTS: In all, 57.6% of aromatase inhibitor-treated and 32.4% of tamoxifen-treated breast cancer patients rated at least 1 vaginal atrophy symptom as moderate/severe, which was significantly more common than in control subjects (P < .01). Aromatase inhibitor-treated patients more often had moderate or severe vaginal atrophy (P < .05), a more atrophic cytohormonal evaluation, and significantly higher vaginal pH (P < .05) than all control subjects, irrespective of hormonal use. CONCLUSION: Our findings indicate that the frequency of vaginal atrophy symptoms, particularly in aromatase inhibitor-treated women, might have been underestimated in previous clinical trials.
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| 5. |
- Kallak, Theodora Kunovac, 1985-, et al.
(författare)
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Aromatase inhibitors affect vaginal proliferation and steroid hormone receptors
- 2014
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Ingår i: Menopause. - : Lippincott Williams & Wilkins. - 1072-3714 .- 1530-0374. ; 21:4, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women with breast cancer who are treated with aromatase inhibitors often experience vaginal atrophy symptoms and sexual dysfunction. This work aims to study proliferation and the presence and distribution of steroid hormone receptors in vaginal biopsies in relation to vaginal atrophy and vaginal pH in women with breast cancer who are on adjuvant endocrine treatment and in healthy postmenopausal women.Methods: This is a cross-sectional study that compares postmenopausal aromatase inhibitor-treated women with breast cancer (n = 15) with tamoxifen-treated women with breast cancer (n = 16) and age-matched postmenopausal women without treatment (n = 19) or with vaginal estrogen therapy (n = 16). Immunohistochemistry was used to study proliferation and steroid hormone receptor staining intensity. Data was correlated with estrogen and androgen levels, vaginal atrophy scores, and vaginal pH.Results: Aromatase inhibitor-treated women had a lower grade of proliferation, weaker progesterone receptor staining, and stronger androgen receptor staining, which correlated with plasma estrone levels, vaginal atrophy scores, and vaginal pH.Conclusions: Women with aromatase inhibitor-treated breast cancer exhibit reduced proliferation and altered steroid hormone receptor staining intensity in the vagina, which are related to clinical signs of vaginal atrophy. Although these effects are most probably attributable to estrogen suppression, a possible local inhibition of aromatase cannot be ruled out.
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| 6. |
- Kallak, Theodora Kunovac, 1985-, et al.
(författare)
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Higher than expected estradiol levels in aromatase inhibitor-treated, postmenopausal breast cancer patients
- 2012
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Ingår i: Climacteric. - London, United Kingdom : Informa Healthcare. - 1369-7137 .- 1473-0804. ; 15:5, s. 473-480
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vaginal estradiol is considered contraindicated in aromatase inhibitor (AI)-treated patients because of the risk of elevated estrogen levels. This leaves limited treatment options for patients experiencing gynecological symptoms. However, in clinical practice, no precise estimation has been performed of circulating estrogens and aromatase index in postmenopausal breast cancer patients on long-lasting AI or tamoxifen treatment.Methods: Steroid hormones were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) and extraction radioimmunoassay (RIA). Postmenopausal AI-treated patients (n =33) were compared with tamoxifen-treated patients (n =34) and controls without vaginal treatment (n =56), with vaginal estradiol (n =25), or with estriol (n =11) treatment.Results: By use of LC-MS/MS, median (range) estradiol plasma concentrations were 16.7 (2.4-162.6), 31.0 (13.4-77.1), 27.2 (7.8-115.8) and 33.3 (20.3-340.1) pmol/l in AI-treated breast cancer patients, tamoxifen-treated breast cancer patients, postmenopausal controls and postmenopausal controls on vaginal estradiol, respectively. The AI-treated group and subgroups had significantly lower estradiol and estrone concentrations than all other groups (p <0.05). There was extensive interindividual variation in estradiol concentration within the AI-treated group, measured using both LC-MS/MS (2.3-182.0 pmol/l) and extraction RIA (2.4-162.6 pmol/l). The AI-treated group had lower aromatase index compared to all other groups (p <0.05-0.001).Conclusion: Circulating estrogen levels may have been underestimated in previous longitudinal studies of AI-treated breast cancer patients. Additional studies are required to further evaluate the role of circulating estrogens in breast cancer patients suffering from gynecological symptoms.
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| 7. |
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| 8. |
- Laanpere, Margit, et al.
(författare)
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Folate-mediated one-carbon metabolism and its effect on female fertility and pregnancy viability
- 2010
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Ingår i: Nutrition reviews. - : Oxford University Press (OUP). - 0029-6643 .- 1753-4887. ; 68:2, s. 99-113
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Forskningsöversikt (refereegranskat)abstract
- This review summarizes current knowledge of the effect of folate-mediated one-carbon metabolism and related genetic variants on female fertility and pregnancy viability. Insufficient folate status disrupts DNA methylation and integrity and increases blood homocysteine levels. Elevated levels of follicular fluid homocysteine correlate with oocyte immaturity and poor early embryo quality, while methylenetetrahydrofolate reductase (MTHFR) gene variants are associated with lower ovarian reserves, diminished response to follicular stimulation, and reduced chance of live birth after in vitro fertilization. Embryos carrying multiple MTHFR variants appear to have a selective disadvantage; however, the heterozygousMTHFR 677CT genotype in the mother and fetus provides the greatest chance for a viable pregnancy and live birth, possibly due to a favorable balance in folate cofactor distribution between methyl donor and nucleotide synthesis. The results of previous studies clearly emphasize that imbalances in folate metabolism and related gene variants may impair female fecundity as well as compromise implantation and the chance of a live birth.
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| 9. |
- Murto, Tiina, et al.
(författare)
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Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility
- 2014
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Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 28:6, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- Folic acid supplements are commonly used by infertile women and lead to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P < 0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P < 0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility.
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| 10. |
- Murto, Tiina, 1975-, et al.
(författare)
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Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to IVF pregnancy outcome
- 2014
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study folic acid intake, folate status and pregnancy outcome after infertility treatment in women with different infertility diagnoses in relation to methylenetetrahydrofolate reductase (MTHFR) 677C>T, 1298A>C and 1793G>A polymorphisms. Also the use of folic acid supplements, folate status and the frequency of different gene variations were studied in women undergoing infertility treatment and fertile women.DESIGN: Observational study.SETTING: University hospital.POPULATION: Women undergoing infertility treatment and healthy, fertile, non-pregnant women.METHODS: A questionnaire was used to assess general background data and use of dietary supplements. Blood samples were taken to determine plasma folate and homocysteine levels, and for genomic DNA extraction. A comparison of four studies was performed to assess pregnancy outcome in relation to MTHFR 677 TT vs. CC, and 1298 CC vs. AA polymorphisms.MAIN OUTCOME MEASURES: Folic acid supplement intake, and plasma folate, homocysteine and genomic assays.RESULTS: Women in the infertility group used significantly more folic acid supplements and had better folate status than fertile women, but pregnancy outcome after fertility treatment was not dependent on folic acid intake, folate status or MTHFR gene variations.CONCLUSION: High folic acid intakes and MTHFR gene variations seem not associated with helping women to achieve pregnancy during or after fertility treatment.
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