Testmiljö
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4/9/2025

Janusmed kön och genus

Janusmed kön och genus – Tamoxifen Ebb

Janusmed kön och genus är ett kunskapsstöd som tillhandahåller information om köns- och genusaspekter på läkemedelsbehandling. Kunskapsstödet är avsedd främst för hälso- och sjukvårdspersonal. Texterna är generella och ska inte ses som behandlingsriktlinjer. Det är alltid behandlande läkare som ansvarar för patientens medicinering.

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Tamoxifen Testmiljö

Tamoxifen

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Produkter

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Nolvadex, Tamoxifen Ebb, Tamoxifen Mylan, Tamoxifen Nordic Drugs, Tamo......

Nolvadex, Tamoxifen Ebb, Tamoxifen Mylan, Tamoxifen Nordic Drugs, Tamoxifen Orifarm, Tamoxifen Sandoz, Tamoxifen Viatris, Tamoxifen-Ratiopharm
ATC-koder

L02BA01

L02BA01
Substanser

tamoxifen, tamoxifencitrat

tamoxifen, tamoxifencitrat
Sammanfattning

Studier har visat på könsskillnader i tamoxifens effekt på neuroendokrin reglering av tillväxthormon och fettmetabolism. Vid bröstcancer har aromatashämmare visats mer effektiva än tamoxifen för postmenopausala kvinnor. Män med bröstcancer som fick adjuvant behandling med tamoxifen hade dock bättre överlevnad än med aromatashämmare.

I lungadenocarcinomcellinjer från kvinnor kan tillväxt blockeras av antiöstrogener. Tillväxt av lungadenocarcinomcellinjer från män kunde dock inte blockeras av antiöstrogener.

Vid melanom sågs bättre överlevnadseffekt av tamoxifen i studier med större andel kvinnor. Om det föreligger några könsskillnader i tamoxifens effekt vid hepatocellulär cancer är oklart.

Studier har visat på könsskillnader i tamoxifens effekt på neuroendokrin reglering av tillväxthormon och fettmetabolism. Vid bröstcancer har aromatashämmare visats mer effektiva än tamoxifen för postmenopausala kvinnor. Män med bröstcancer som fick adjuvant behandling med tamoxifen hade dock bättre överlevnad än med aromatashämmare. I lungadenocarcinomcellinjer från kvinnor kan tillväxt blockeras av antiöstrogener. Tillväxt av lungadenocarcinomcellinjer från män kunde dock inte blockeras av antiöstrogener. Vid melanom sågs bättre överlevnadseffekt av tamoxifen i studier med större andel kvinnor. Om det föreligger några könsskillnader i tamoxifens effekt vid hepatocellulär cancer är oklart.
Background

Tamoxifen is a selective estrogen receptor modulator, indicated for the palliative and adjuvant treatment of estrogen receptor positive breast cancer. However, it has also been used in patients with lung adenocarcinoma, hepatocellular carcinoma, melanoma, McCune Albright syndrome in children, and pubertal gynecomastia [1, 2].

Pharmacokinetics and dosing
Controlled studies on differences between men and women regarding pharmacokinetics of tamoxifen are lacking. Different dosing between men and women is not recommended by the pharmaceutical company [3].




Effects
Breast cancer

It is known that there are substantial differences in the etiology of female and male breast cancer, with the latter arising more frequently as a result of BRCA2 gene mutations with differential effects of single nucleotide polymorphisms by patient’s sex, among other molecular profile differences [4]. Luminal A is the predominant subtype in men, which is rarely of basal cell types and never HER2 positive [4].

It has been seen that aromatase inhibitors (AI) are more effective than tamoxifen in postmen......

Visa hela bakgrundstexten

Tamoxifen is a selective estrogen receptor modulator, indicated for the palliative and adjuvant treatment of estrogen receptor positive breast cancer. However, it has also been used in patients with lung adenocarcinoma, hepatocellular carcinoma, melanoma, McCune Albright syndrome in children, and pubertal gynecomastia [1, 2]. # Pharmacokinetics and dosing Controlled studies on differences between men and women regarding pharmacokinetics of tamoxifen are lacking. Different dosing between men and women is not recommended by the pharmaceutical company [3]. # # Effects **Breast cancer** It is known that there are substantial differences in the etiology of female and male breast cancer, with the latter arising more frequently as a result of BRCA2 gene mutations with differential effects of single nucleotide polymorphisms by patient’s sex, among other molecular profile differences [4]. Luminal A is the predominant subtype in men, which is rarely of basal cell types and never HER2 positive [4]. It has been seen that aromatase inhibitors (AI) are more effective than tamoxifen in postmenopausal women [5-8], thus it was suggested that the same could be true in men with breast cancer. A study published in 1978 was the first to report a beneficial effect of tamoxifen in metastatic male breast cancer with all 3 patients gaining responses lasting for >6 months [9]. There have been several studies showing variable results on AI and tamoxifen treated male breast cancer [10-17]. In a multicenter study of 31 men with metastatic breast cancer treated with tamoxifen, complete or partial response occurred in 15 (48%) [10]. A retrospective study (257 men, 2785 women) treated with hormonal therapy (316 women and 158 men treated with tamoxifen), showed that the 5-year overall survival in tamoxifen treated patients was similar in women and men (85.1% and 89.2% respectively) [18]. In contrast, AI treatment was associated with poorer survival of men with breast cancer compared to women [18]. After a median follow-up of 42 months, those treated with AI had a 1.5-fold increased mortality rate compared with those treated with tamoxifen [18]. There have been no randomized trials of adjuvant or palliative chemotherapy in men with breast cancer and the reported series have been small, with variations in regimens and dosage. Thus, no conclusions can be drawn regarding the role of tamoxifen for men with breast cancer. **Neuroendocrine regulation** In a randomized trial (10 healthy postmenopausal women, 10 healthy men), tamoxifen attenuated growth hormone (GH) response to stimulation with arginine in women, but not in men. The overall reduction in GH response in women by the higher dose of tamoxifen (20 mg) was 88%. On the other hand, tamoxifen reduced mean insulin-like growth factor 1 (IGF-I) levels and increased sex hormone binding globulin (SHBG) levels in both women and men. This effect on circulating IGF-I levels was not different between men and women, whereas its effect on SHBG was greater in women. In men, tamoxifen increased luteinizing hormone (LH) and testosterone concentrations in a dose-dependent manner [4]. Similarly, another study (10 healthy postmenopausal women, 10 healthy men) found that the suppressive effect of tamoxifen on fat metabolism is sex-dependent. The study showed that tamoxifen significantly reduced the mean GH response to arginine stimulation, the circulating IGF-I levels, postprandial fat oxidation and carbohydrate oxidation in women [5]. Whereas in men, tamoxifen did not affect the GH response to stimulation but reduced mean IGF-I levels and increased mean testosterone levels. Furthermore, fat and carbohydrate oxidation were not affected by tamoxifen in men [5]. In women and men, tamoxifen did not change serum levels of total cholesterol, HDL, or glucose. In men opposite to in women, tamoxifen reduced triglyceride levels [5]. **Lung cancer** A bioinformatics analysis (gene expression data were collected from 2352 men and 1751 women) of sex-linked molecular alterations and therapies in cancer predicted that women are sensitive, and men are resistant to tamoxifen treatment of lung adenocarcinoma [21]. A study showed that lung adenocarcinoma cell lines from women proliferated in response to E2, and that growth was blocked by antiestrogens. In contrast, lung adenocarcinoma cells from men were not responsive to E2 or antiestrogens [22]. **Melanoma** Androgens, estrogens, and their receptors, are involved in signaling of commonly mutated melanoma pathways, thus it is a hormone-sensitive tumor. For this reason, tamoxifen has been considered as a possible therapy for melanoma [23]. A meta-analysis on tamoxifen treatment for advanced melanoma, including 9 studies (764 men, 526 women), showed a tendency towards benefit of tamoxifen in the group with higher women/men ratio. The treatment effect was consistent regardless of the dose or sex of participants, however, a greater benefit in response towards tamoxifen was seen in trials with female predominance [24]. **Hepatocellular carcinoma** In a systematic review including 10 trials on tamoxifen treatment in patients with hepatocellular carcinoma (in total 1709 patients), most patients were men in all studies (range, 71-89%). The influence of patient’s sex on treatment effects was not a primary objective in any of the trials [25]. One trial reported no difference in survival between men and women in post-hoc analysis [26]. Another trial reported a benefit of tamoxifen for men without major hepatic insufficiency, but no benefit for women [26-27]. # Adverse effects Bone loss has been seen in premenopausal women, but not in men [3]. In men, the most commonly reported adverse events in retrospective studies and reviews have been loss of libido, weight gain, hot flushes and mood alterations [28-32]. The dual attenuation of GH secretion and hepatic IGF-I production indicates that tamoxifen may induce a GH deficiency, and it is known that this condition can lead to hepatic steatosis that can progress to severe liver disease [33, 34]. Hepatic steatosis has been described as a frequent and reversible adverse effect of tamoxifen treatment in breast cancer patients [35], but the mechanism remains unclear. Even though the sample size of the studies is small, the authors suggest that women could be at greater risk than men [3, 4]. # Reproductive health issues Tamoxifen can inhibit menstruation in some premenopausal women [3]. Pregnancy should be avoided in women of childbearing potential on tamoxifen treatment and within two months after treatment. Non-hormonal contraceptive methods is recommended for women of childbearing potential [3]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Försäljning på recept

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Fler kvinnor än män hämtade ut läkemedel innehållande tamoxifen (ATC-kod L02BA01) på recept i Sverige år 2019, totalt 17 378 kvinnor och 800 män. Det motsvarar 3,5 respektive 0,2 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-79 år hos kvinnor och 85 år och äldre hos män. I genomsnitt var läkemedel innehållande tamoxifen 32 gånger vanligare bland kvinnor [36].
Referenser

Visa referenser

  1. Neyman A, Eugster EA. Treatment of Girls and Boys with McCune-Albright Syndrome with Precocious Puberty - Update 2017. Pediatr Endocrinol Rev. 2017;15(2):136-141.

  2. Zehetner A. Tamoxifen to treat male pubertal gynaecomastia. Int J Pediatr Adolesc Med. 2015;2(3):152-156.

  3. Tamoxifen Sandoz (tamoxifen). Summary of Prodruct Characteristics. Swedish Medical Products Agency [updated 2018-06-13, cited 2019-10-03].

  4. Fentiman IS. Male breast cancer is not congruent with the female disease. Crit Rev Oncol Hematol. 2016;101(1):119-24.

  5. Untch M, Gerber B, Harbeck N, Jackisch C, Marschner N, Möbus V et al. 13th st Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus - opinion of a german team of experts (zurich 2013). Breast Care (Basel). 2013;8(3):221-9.

  6. Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010;11(12):1135-41.

  7. Ingle JN, Tu D, Pater JL, Muss HB, Martino S, Robert NJ et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA17. Ann Oncol. 2008;19(5):877-82.

  8. Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ et al. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18(9):1211-1220.

  9. Cantwell BM, Tong D, Minton M, Rubens RD, Hayward JL. Tamoxifen and male breast cancer. Lancet. 1978;2(8089):582-3.

  10. Patterson JS, Battersby LA, Bach BK. Use of tamoxifen in advanced male breast cancer. Cancer Treat Rep. 1980;64(6):801-4.

  11. Ribeiro GG. The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast. Br J Cancer. 1976;33(4):465-7.

  12. Bezwoda WR, Hesdorffer C, Dansey R, de Moor N, Derman DP, Browde S et al. Breast cancer in men Clinical features, hormone receptor status, and response to therapy. Cancer. 1987;60(6):1337-40.

  13. Italiano A, Largillier R, Marcy PY, Foa C, Ferrero JM, Hartmann MT et al. [Complete remission obtained with letrozole in a man with metastatic breast cancer]. Rev Med Interne. 2004;25(4):323-4.

  14. Arriola E, Hui E, Dowsett M, Smith IE. Aromatase inhibitors and male breast cancer. Clin Transl Oncol. 2007;9(3):192-4.

  15. Di Lauro L, Vici P, Del Medico P, Laudadio L, Tomao S, Giannarelli D et al. Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer. Breast Cancer Res Treat. 2013;141(1):119-23.

  16. Zagouri F, Sergentanis TN, Koutoulidis V, Sparber C, Steger GG, Dubsky P et al. Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer. 2013;108(11):2259-63.

  17. Doyen J, Italiano A, Largillier R, Ferrero JM, Fontana X, Thyss A. Aromatase inhibition in male breast cancer patients: biological and clinical implications. Ann Oncol. 2010;21(6):1243-5.

  18. Eggemann H, Altmann U, Costa SD, Ignatov A. Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer. J Cancer Res Clin Oncol. 2018;144(2):337-341.

  19. Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y et al. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int. 2007;1(2):287-94.

  20. Nishino M, Hayakawa K, Nakamura Y, Morimoto T, Mukaihara S. Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: high frequency of involvement and rapid reversal after completion of tamoxifen therapy. AJR Am J Roentgenol. 2003;180(1):129-34.

  21. Ma J, Malladi S, Beck AH. Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer. Sci Rep. 2016;6(1):19119.

  22. Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM. Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells. Am J Respir Cell Mol Biol. 2010;42(3):320-30.

  23. Mitkov M, Joseph R, Copland J. Steroid hormone influence on melanomagenesis. Mol Cell Endocrinol. 2015;417(1):94-102.

  24. Beguerie JR, Xingzhong J, Valdez RP. Tamoxifen vs non-tamoxifen treatment for advanced melanoma: a meta-analysis. Int J Dermatol. 2010;49(10):1194-202.

  25. Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma A systematic review. Cancer. 2005;103(7):1408-14.

  26. Castells A, Bruix J, Brú C, Ayuso C, Roca M, Boix L et al. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Gastroenterology. 1995;109(3):917-22.

  27. Barbare J‐C, Milan C, Bouché O, et al. Treatment of advanced hepatocellular carcinoma (HCC) with tamoxifen: a phase III trial in 420 patients [abstract 551]. Proc Am Soc Clin Oncol. 2002;21(1):138A.

  28. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459-78.

  29. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21(4):602-6.

  30. Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI. Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer. 1994;74(1):74-7.

  31. Visram H, Kanji F, Dent SF. Endocrine therapy for male breast cancer: rates of toxicity and adherence. Curr Oncol. 2010;17(5):17-21.

  32. Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH. Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol. 2012;23(6):1471-4.

  33. Birzniece V, Sutanto S, Ho KK. Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators. J Clin Endocrinol Metab. 2012;97(4):E521-7.

  34. Birzniece V, Ho KK. Estrogen receptor antagonism uncovers gender-dimorphic suppression of whole body fat oxidation in humans: differential effects of tamoxifen on the GH and gonadal axes. Eur J Endocrinol. 2015;173(4):479-87.

  35. Takahashi Y, Iida K, Takahashi K, Yoshioka S, Fukuoka H, Takeno R et al. Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency. Gastroenterology. 2007;132(3):938-43.

  36. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-10-29.]

  1. Neyman A, Eugster EA. Treatment of Girls and Boys with McCune-Albright Syndrome with Precocious Puberty - Update 2017. Pediatr Endocrinol Rev. 2017;15(2):136-141.
  2. Zehetner A. Tamoxifen to treat male pubertal gynaecomastia. Int J Pediatr Adolesc Med. 2015;2(3):152-156.
  3. Tamoxifen Sandoz (tamoxifen). Summary of Prodruct Characteristics. Swedish Medical Products Agency [updated 2018-06-13, cited 2019-10-03].
  4. Fentiman IS. Male breast cancer is not congruent with the female disease. Crit Rev Oncol Hematol. 2016;101(1):119-24.
  5. Untch M, Gerber B, Harbeck N, Jackisch C, Marschner N, Möbus V et al. 13th st Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus - opinion of a german team of experts (zurich 2013). Breast Care (Basel). 2013;8(3):221-9.
  6. Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010;11(12):1135-41.
  7. Ingle JN, Tu D, Pater JL, Muss HB, Martino S, Robert NJ et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA17. Ann Oncol. 2008;19(5):877-82.
  8. Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ et al. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18(9):1211-1220.
  9. Cantwell BM, Tong D, Minton M, Rubens RD, Hayward JL. Tamoxifen and male breast cancer. Lancet. 1978;2(8089):582-3.
  10. Patterson JS, Battersby LA, Bach BK. Use of tamoxifen in advanced male breast cancer. Cancer Treat Rep. 1980;64(6):801-4.
  11. Ribeiro GG. The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast. Br J Cancer. 1976;33(4):465-7.
  12. Bezwoda WR, Hesdorffer C, Dansey R, de Moor N, Derman DP, Browde S et al. Breast cancer in men Clinical features, hormone receptor status, and response to therapy. Cancer. 1987;60(6):1337-40.
  13. Italiano A, Largillier R, Marcy PY, Foa C, Ferrero JM, Hartmann MT et al. [Complete remission obtained with letrozole in a man with metastatic breast cancer]. Rev Med Interne. 2004;25(4):323-4.
  14. Arriola E, Hui E, Dowsett M, Smith IE. Aromatase inhibitors and male breast cancer. Clin Transl Oncol. 2007;9(3):192-4.
  15. Di Lauro L, Vici P, Del Medico P, Laudadio L, Tomao S, Giannarelli D et al. Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer. Breast Cancer Res Treat. 2013;141(1):119-23.
  16. Zagouri F, Sergentanis TN, Koutoulidis V, Sparber C, Steger GG, Dubsky P et al. Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer. 2013;108(11):2259-63.
  17. Doyen J, Italiano A, Largillier R, Ferrero JM, Fontana X, Thyss A. Aromatase inhibition in male breast cancer patients: biological and clinical implications. Ann Oncol. 2010;21(6):1243-5.
  18. Eggemann H, Altmann U, Costa SD, Ignatov A. Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer. J Cancer Res Clin Oncol. 2018;144(2):337-341.
  19. Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y et al. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int. 2007;1(2):287-94.
  20. Nishino M, Hayakawa K, Nakamura Y, Morimoto T, Mukaihara S. Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: high frequency of involvement and rapid reversal after completion of tamoxifen therapy. AJR Am J Roentgenol. 2003;180(1):129-34.
  21. Ma J, Malladi S, Beck AH. Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer. Sci Rep. 2016;6(1):19119.
  22. Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM. Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells. Am J Respir Cell Mol Biol. 2010;42(3):320-30.
  23. Mitkov M, Joseph R, Copland J. Steroid hormone influence on melanomagenesis. Mol Cell Endocrinol. 2015;417(1):94-102.
  24. Beguerie JR, Xingzhong J, Valdez RP. Tamoxifen vs non-tamoxifen treatment for advanced melanoma: a meta-analysis. Int J Dermatol. 2010;49(10):1194-202.
  25. Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma A systematic review. Cancer. 2005;103(7):1408-14.
  26. Castells A, Bruix J, Brú C, Ayuso C, Roca M, Boix L et al. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Gastroenterology. 1995;109(3):917-22.
  27. Barbare J‐C, Milan C, Bouché O, et al. Treatment of advanced hepatocellular carcinoma (HCC) with tamoxifen: a phase III trial in 420 patients [abstract 551]. Proc Am Soc Clin Oncol. 2002;21(1):138A.
  28. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459-78.
  29. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21(4):602-6.
  30. Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI. Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer. 1994;74(1):74-7.
  31. Visram H, Kanji F, Dent SF. Endocrine therapy for male breast cancer: rates of toxicity and adherence. Curr Oncol. 2010;17(5):17-21.
  32. Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH. Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol. 2012;23(6):1471-4.
  33. Birzniece V, Sutanto S, Ho KK. Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators. J Clin Endocrinol Metab. 2012;97(4):E521-7.
  34. Birzniece V, Ho KK. Estrogen receptor antagonism uncovers gender-dimorphic suppression of whole body fat oxidation in humans: differential effects of tamoxifen on the GH and gonadal axes. Eur J Endocrinol. 2015;173(4):479-87.
  35. Takahashi Y, Iida K, Takahashi K, Yoshioka S, Fukuoka H, Takeno R et al. Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency. Gastroenterology. 2007;132(3):938-43.
  36. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-10-29.]
Uppdaterat

Litteratursökningsdatum: 10/3/2019

Litteratursökningsdatum: 10/3/2019
Fasstexter

Visa fasstexter

C C
C C

Tamoxifen Testmiljö

Tamoxifen

Klass : C

Visa all info

Skriv ut

Kontakta oss

Produkter

Visa alla produkter

Nolvadex, Tamoxifen Ebb, Tamoxifen Mylan, Tamoxifen Nordic Drugs, Tamo......

Nolvadex, Tamoxifen Ebb, Tamoxifen Mylan, Tamoxifen Nordic Drugs, Tamoxifen Orifarm, Tamoxifen Sandoz, Tamoxifen Viatris, Tamoxifen-Ratiopharm
ATC-koder

L02BA01

L02BA01
Substanser

tamoxifen, tamoxifencitrat

tamoxifen, tamoxifencitrat
Sammanfattning

Studier har visat på könsskillnader i tamoxifens effekt på neuroendokrin reglering av tillväxthormon och fettmetabolism. Vid bröstcancer har aromatashämmare visats mer effektiva än tamoxifen för postmenopausala kvinnor. Män med bröstcancer som fick adjuvant behandling med tamoxifen hade dock bättre överlevnad än med aromatashämmare.

I lungadenocarcinomcellinjer från kvinnor kan tillväxt blockeras av antiöstrogener. Tillväxt av lungadenocarcinomcellinjer från män kunde dock inte blockeras av antiöstrogener.

Vid melanom sågs bättre överlevnadseffekt av tamoxifen i studier med större andel kvinnor. Om det föreligger några könsskillnader i tamoxifens effekt vid hepatocellulär cancer är oklart.

Studier har visat på könsskillnader i tamoxifens effekt på neuroendokrin reglering av tillväxthormon och fettmetabolism. Vid bröstcancer har aromatashämmare visats mer effektiva än tamoxifen för postmenopausala kvinnor. Män med bröstcancer som fick adjuvant behandling med tamoxifen hade dock bättre överlevnad än med aromatashämmare. I lungadenocarcinomcellinjer från kvinnor kan tillväxt blockeras av antiöstrogener. Tillväxt av lungadenocarcinomcellinjer från män kunde dock inte blockeras av antiöstrogener. Vid melanom sågs bättre överlevnadseffekt av tamoxifen i studier med större andel kvinnor. Om det föreligger några könsskillnader i tamoxifens effekt vid hepatocellulär cancer är oklart.
Background

Tamoxifen is a selective estrogen receptor modulator, indicated for the palliative and adjuvant treatment of estrogen receptor positive breast cancer. However, it has also been used in patients with lung adenocarcinoma, hepatocellular carcinoma, melanoma, McCune Albright syndrome in children, and pubertal gynecomastia [1, 2].

Pharmacokinetics and dosing
Controlled studies on differences between men and women regarding pharmacokinetics of tamoxifen are lacking. Different dosing between men and women is not recommended by the pharmaceutical company [3].




Effects
Breast cancer

It is known that there are substantial differences in the etiology of female and male breast cancer, with the latter arising more frequently as a result of BRCA2 gene mutations with differential effects of single nucleotide polymorphisms by patient’s sex, among other molecular profile differences [4]. Luminal A is the predominant subtype in men, which is rarely of basal cell types and never HER2 positive [4].

It has been seen that aromatase inhibitors (AI) are more effective than tamoxifen in postmen......

Visa hela bakgrundstexten

Tamoxifen is a selective estrogen receptor modulator, indicated for the palliative and adjuvant treatment of estrogen receptor positive breast cancer. However, it has also been used in patients with lung adenocarcinoma, hepatocellular carcinoma, melanoma, McCune Albright syndrome in children, and pubertal gynecomastia [1, 2]. # Pharmacokinetics and dosing Controlled studies on differences between men and women regarding pharmacokinetics of tamoxifen are lacking. Different dosing between men and women is not recommended by the pharmaceutical company [3]. # # Effects **Breast cancer** It is known that there are substantial differences in the etiology of female and male breast cancer, with the latter arising more frequently as a result of BRCA2 gene mutations with differential effects of single nucleotide polymorphisms by patient’s sex, among other molecular profile differences [4]. Luminal A is the predominant subtype in men, which is rarely of basal cell types and never HER2 positive [4]. It has been seen that aromatase inhibitors (AI) are more effective than tamoxifen in postmenopausal women [5-8], thus it was suggested that the same could be true in men with breast cancer. A study published in 1978 was the first to report a beneficial effect of tamoxifen in metastatic male breast cancer with all 3 patients gaining responses lasting for >6 months [9]. There have been several studies showing variable results on AI and tamoxifen treated male breast cancer [10-17]. In a multicenter study of 31 men with metastatic breast cancer treated with tamoxifen, complete or partial response occurred in 15 (48%) [10]. A retrospective study (257 men, 2785 women) treated with hormonal therapy (316 women and 158 men treated with tamoxifen), showed that the 5-year overall survival in tamoxifen treated patients was similar in women and men (85.1% and 89.2% respectively) [18]. In contrast, AI treatment was associated with poorer survival of men with breast cancer compared to women [18]. After a median follow-up of 42 months, those treated with AI had a 1.5-fold increased mortality rate compared with those treated with tamoxifen [18]. There have been no randomized trials of adjuvant or palliative chemotherapy in men with breast cancer and the reported series have been small, with variations in regimens and dosage. Thus, no conclusions can be drawn regarding the role of tamoxifen for men with breast cancer. **Neuroendocrine regulation** In a randomized trial (10 healthy postmenopausal women, 10 healthy men), tamoxifen attenuated growth hormone (GH) response to stimulation with arginine in women, but not in men. The overall reduction in GH response in women by the higher dose of tamoxifen (20 mg) was 88%. On the other hand, tamoxifen reduced mean insulin-like growth factor 1 (IGF-I) levels and increased sex hormone binding globulin (SHBG) levels in both women and men. This effect on circulating IGF-I levels was not different between men and women, whereas its effect on SHBG was greater in women. In men, tamoxifen increased luteinizing hormone (LH) and testosterone concentrations in a dose-dependent manner [4]. Similarly, another study (10 healthy postmenopausal women, 10 healthy men) found that the suppressive effect of tamoxifen on fat metabolism is sex-dependent. The study showed that tamoxifen significantly reduced the mean GH response to arginine stimulation, the circulating IGF-I levels, postprandial fat oxidation and carbohydrate oxidation in women [5]. Whereas in men, tamoxifen did not affect the GH response to stimulation but reduced mean IGF-I levels and increased mean testosterone levels. Furthermore, fat and carbohydrate oxidation were not affected by tamoxifen in men [5]. In women and men, tamoxifen did not change serum levels of total cholesterol, HDL, or glucose. In men opposite to in women, tamoxifen reduced triglyceride levels [5]. **Lung cancer** A bioinformatics analysis (gene expression data were collected from 2352 men and 1751 women) of sex-linked molecular alterations and therapies in cancer predicted that women are sensitive, and men are resistant to tamoxifen treatment of lung adenocarcinoma [21]. A study showed that lung adenocarcinoma cell lines from women proliferated in response to E2, and that growth was blocked by antiestrogens. In contrast, lung adenocarcinoma cells from men were not responsive to E2 or antiestrogens [22]. **Melanoma** Androgens, estrogens, and their receptors, are involved in signaling of commonly mutated melanoma pathways, thus it is a hormone-sensitive tumor. For this reason, tamoxifen has been considered as a possible therapy for melanoma [23]. A meta-analysis on tamoxifen treatment for advanced melanoma, including 9 studies (764 men, 526 women), showed a tendency towards benefit of tamoxifen in the group with higher women/men ratio. The treatment effect was consistent regardless of the dose or sex of participants, however, a greater benefit in response towards tamoxifen was seen in trials with female predominance [24]. **Hepatocellular carcinoma** In a systematic review including 10 trials on tamoxifen treatment in patients with hepatocellular carcinoma (in total 1709 patients), most patients were men in all studies (range, 71-89%). The influence of patient’s sex on treatment effects was not a primary objective in any of the trials [25]. One trial reported no difference in survival between men and women in post-hoc analysis [26]. Another trial reported a benefit of tamoxifen for men without major hepatic insufficiency, but no benefit for women [26-27]. # Adverse effects Bone loss has been seen in premenopausal women, but not in men [3]. In men, the most commonly reported adverse events in retrospective studies and reviews have been loss of libido, weight gain, hot flushes and mood alterations [28-32]. The dual attenuation of GH secretion and hepatic IGF-I production indicates that tamoxifen may induce a GH deficiency, and it is known that this condition can lead to hepatic steatosis that can progress to severe liver disease [33, 34]. Hepatic steatosis has been described as a frequent and reversible adverse effect of tamoxifen treatment in breast cancer patients [35], but the mechanism remains unclear. Even though the sample size of the studies is small, the authors suggest that women could be at greater risk than men [3, 4]. # Reproductive health issues Tamoxifen can inhibit menstruation in some premenopausal women [3]. Pregnancy should be avoided in women of childbearing potential on tamoxifen treatment and within two months after treatment. Non-hormonal contraceptive methods is recommended for women of childbearing potential [3]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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Fler kvinnor än män hämtade ut läkemedel innehållande tamoxifen (ATC-kod L02BA01) på recept i Sverige år 2019, totalt 17 378 kvinnor och 800 män. Det motsvarar 3,5 respektive 0,2 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-79 år hos kvinnor och 85 år och äldre hos män. I genomsnitt var läkemedel innehållande tamoxifen 32 gånger vanligare bland kvinnor [36].
Referenser

Visa referenser

  1. Neyman A, Eugster EA. Treatment of Girls and Boys with McCune-Albright Syndrome with Precocious Puberty - Update 2017. Pediatr Endocrinol Rev. 2017;15(2):136-141.

  2. Zehetner A. Tamoxifen to treat male pubertal gynaecomastia. Int J Pediatr Adolesc Med. 2015;2(3):152-156.

  3. Tamoxifen Sandoz (tamoxifen). Summary of Prodruct Characteristics. Swedish Medical Products Agency [updated 2018-06-13, cited 2019-10-03].

  4. Fentiman IS. Male breast cancer is not congruent with the female disease. Crit Rev Oncol Hematol. 2016;101(1):119-24.

  5. Untch M, Gerber B, Harbeck N, Jackisch C, Marschner N, Möbus V et al. 13th st Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus - opinion of a german team of experts (zurich 2013). Breast Care (Basel). 2013;8(3):221-9.

  6. Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010;11(12):1135-41.

  7. Ingle JN, Tu D, Pater JL, Muss HB, Martino S, Robert NJ et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA17. Ann Oncol. 2008;19(5):877-82.

  8. Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ et al. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18(9):1211-1220.

  9. Cantwell BM, Tong D, Minton M, Rubens RD, Hayward JL. Tamoxifen and male breast cancer. Lancet. 1978;2(8089):582-3.

  10. Patterson JS, Battersby LA, Bach BK. Use of tamoxifen in advanced male breast cancer. Cancer Treat Rep. 1980;64(6):801-4.

  11. Ribeiro GG. The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast. Br J Cancer. 1976;33(4):465-7.

  12. Bezwoda WR, Hesdorffer C, Dansey R, de Moor N, Derman DP, Browde S et al. Breast cancer in men Clinical features, hormone receptor status, and response to therapy. Cancer. 1987;60(6):1337-40.

  13. Italiano A, Largillier R, Marcy PY, Foa C, Ferrero JM, Hartmann MT et al. [Complete remission obtained with letrozole in a man with metastatic breast cancer]. Rev Med Interne. 2004;25(4):323-4.

  14. Arriola E, Hui E, Dowsett M, Smith IE. Aromatase inhibitors and male breast cancer. Clin Transl Oncol. 2007;9(3):192-4.

  15. Di Lauro L, Vici P, Del Medico P, Laudadio L, Tomao S, Giannarelli D et al. Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer. Breast Cancer Res Treat. 2013;141(1):119-23.

  16. Zagouri F, Sergentanis TN, Koutoulidis V, Sparber C, Steger GG, Dubsky P et al. Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer. 2013;108(11):2259-63.

  17. Doyen J, Italiano A, Largillier R, Ferrero JM, Fontana X, Thyss A. Aromatase inhibition in male breast cancer patients: biological and clinical implications. Ann Oncol. 2010;21(6):1243-5.

  18. Eggemann H, Altmann U, Costa SD, Ignatov A. Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer. J Cancer Res Clin Oncol. 2018;144(2):337-341.

  19. Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y et al. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int. 2007;1(2):287-94.

  20. Nishino M, Hayakawa K, Nakamura Y, Morimoto T, Mukaihara S. Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: high frequency of involvement and rapid reversal after completion of tamoxifen therapy. AJR Am J Roentgenol. 2003;180(1):129-34.

  21. Ma J, Malladi S, Beck AH. Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer. Sci Rep. 2016;6(1):19119.

  22. Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM. Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells. Am J Respir Cell Mol Biol. 2010;42(3):320-30.

  23. Mitkov M, Joseph R, Copland J. Steroid hormone influence on melanomagenesis. Mol Cell Endocrinol. 2015;417(1):94-102.

  24. Beguerie JR, Xingzhong J, Valdez RP. Tamoxifen vs non-tamoxifen treatment for advanced melanoma: a meta-analysis. Int J Dermatol. 2010;49(10):1194-202.

  25. Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma A systematic review. Cancer. 2005;103(7):1408-14.

  26. Castells A, Bruix J, Brú C, Ayuso C, Roca M, Boix L et al. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Gastroenterology. 1995;109(3):917-22.

  27. Barbare J‐C, Milan C, Bouché O, et al. Treatment of advanced hepatocellular carcinoma (HCC) with tamoxifen: a phase III trial in 420 patients [abstract 551]. Proc Am Soc Clin Oncol. 2002;21(1):138A.

  28. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459-78.

  29. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21(4):602-6.

  30. Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI. Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer. 1994;74(1):74-7.

  31. Visram H, Kanji F, Dent SF. Endocrine therapy for male breast cancer: rates of toxicity and adherence. Curr Oncol. 2010;17(5):17-21.

  32. Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH. Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol. 2012;23(6):1471-4.

  33. Birzniece V, Sutanto S, Ho KK. Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators. J Clin Endocrinol Metab. 2012;97(4):E521-7.

  34. Birzniece V, Ho KK. Estrogen receptor antagonism uncovers gender-dimorphic suppression of whole body fat oxidation in humans: differential effects of tamoxifen on the GH and gonadal axes. Eur J Endocrinol. 2015;173(4):479-87.

  35. Takahashi Y, Iida K, Takahashi K, Yoshioka S, Fukuoka H, Takeno R et al. Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency. Gastroenterology. 2007;132(3):938-43.

  36. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-10-29.]

  1. Neyman A, Eugster EA. Treatment of Girls and Boys with McCune-Albright Syndrome with Precocious Puberty - Update 2017. Pediatr Endocrinol Rev. 2017;15(2):136-141.
  2. Zehetner A. Tamoxifen to treat male pubertal gynaecomastia. Int J Pediatr Adolesc Med. 2015;2(3):152-156.
  3. Tamoxifen Sandoz (tamoxifen). Summary of Prodruct Characteristics. Swedish Medical Products Agency [updated 2018-06-13, cited 2019-10-03].
  4. Fentiman IS. Male breast cancer is not congruent with the female disease. Crit Rev Oncol Hematol. 2016;101(1):119-24.
  5. Untch M, Gerber B, Harbeck N, Jackisch C, Marschner N, Möbus V et al. 13th st Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus - opinion of a german team of experts (zurich 2013). Breast Care (Basel). 2013;8(3):221-9.
  6. Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010;11(12):1135-41.
  7. Ingle JN, Tu D, Pater JL, Muss HB, Martino S, Robert NJ et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA17. Ann Oncol. 2008;19(5):877-82.
  8. Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ et al. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18(9):1211-1220.
  9. Cantwell BM, Tong D, Minton M, Rubens RD, Hayward JL. Tamoxifen and male breast cancer. Lancet. 1978;2(8089):582-3.
  10. Patterson JS, Battersby LA, Bach BK. Use of tamoxifen in advanced male breast cancer. Cancer Treat Rep. 1980;64(6):801-4.
  11. Ribeiro GG. The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast. Br J Cancer. 1976;33(4):465-7.
  12. Bezwoda WR, Hesdorffer C, Dansey R, de Moor N, Derman DP, Browde S et al. Breast cancer in men Clinical features, hormone receptor status, and response to therapy. Cancer. 1987;60(6):1337-40.
  13. Italiano A, Largillier R, Marcy PY, Foa C, Ferrero JM, Hartmann MT et al. [Complete remission obtained with letrozole in a man with metastatic breast cancer]. Rev Med Interne. 2004;25(4):323-4.
  14. Arriola E, Hui E, Dowsett M, Smith IE. Aromatase inhibitors and male breast cancer. Clin Transl Oncol. 2007;9(3):192-4.
  15. Di Lauro L, Vici P, Del Medico P, Laudadio L, Tomao S, Giannarelli D et al. Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer. Breast Cancer Res Treat. 2013;141(1):119-23.
  16. Zagouri F, Sergentanis TN, Koutoulidis V, Sparber C, Steger GG, Dubsky P et al. Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer. 2013;108(11):2259-63.
  17. Doyen J, Italiano A, Largillier R, Ferrero JM, Fontana X, Thyss A. Aromatase inhibition in male breast cancer patients: biological and clinical implications. Ann Oncol. 2010;21(6):1243-5.
  18. Eggemann H, Altmann U, Costa SD, Ignatov A. Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer. J Cancer Res Clin Oncol. 2018;144(2):337-341.
  19. Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y et al. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int. 2007;1(2):287-94.
  20. Nishino M, Hayakawa K, Nakamura Y, Morimoto T, Mukaihara S. Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: high frequency of involvement and rapid reversal after completion of tamoxifen therapy. AJR Am J Roentgenol. 2003;180(1):129-34.
  21. Ma J, Malladi S, Beck AH. Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer. Sci Rep. 2016;6(1):19119.
  22. Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM. Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells. Am J Respir Cell Mol Biol. 2010;42(3):320-30.
  23. Mitkov M, Joseph R, Copland J. Steroid hormone influence on melanomagenesis. Mol Cell Endocrinol. 2015;417(1):94-102.
  24. Beguerie JR, Xingzhong J, Valdez RP. Tamoxifen vs non-tamoxifen treatment for advanced melanoma: a meta-analysis. Int J Dermatol. 2010;49(10):1194-202.
  25. Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma A systematic review. Cancer. 2005;103(7):1408-14.
  26. Castells A, Bruix J, Brú C, Ayuso C, Roca M, Boix L et al. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Gastroenterology. 1995;109(3):917-22.
  27. Barbare J‐C, Milan C, Bouché O, et al. Treatment of advanced hepatocellular carcinoma (HCC) with tamoxifen: a phase III trial in 420 patients [abstract 551]. Proc Am Soc Clin Oncol. 2002;21(1):138A.
  28. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459-78.
  29. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21(4):602-6.
  30. Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI. Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer. 1994;74(1):74-7.
  31. Visram H, Kanji F, Dent SF. Endocrine therapy for male breast cancer: rates of toxicity and adherence. Curr Oncol. 2010;17(5):17-21.
  32. Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH. Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol. 2012;23(6):1471-4.
  33. Birzniece V, Sutanto S, Ho KK. Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators. J Clin Endocrinol Metab. 2012;97(4):E521-7.
  34. Birzniece V, Ho KK. Estrogen receptor antagonism uncovers gender-dimorphic suppression of whole body fat oxidation in humans: differential effects of tamoxifen on the GH and gonadal axes. Eur J Endocrinol. 2015;173(4):479-87.
  35. Takahashi Y, Iida K, Takahashi K, Yoshioka S, Fukuoka H, Takeno R et al. Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency. Gastroenterology. 2007;132(3):938-43.
  36. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-10-29.]
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Litteratursökningsdatum: 10/3/2019

Litteratursökningsdatum: 10/3/2019
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