- Email: [email protected]
A proposed mechanism for the pathogenesis of multiple primary tumours
624
Correspondence / Medical Hypotheses 73 (2009) 623–631
hookah might act as an anti-oxidant against a category of short half-life free radicals [25]. On the other hand, scientists have calculated the reduction rate of free radicals in a cigarette that primarily heats tobacco. Interestingly, this product (Eclipse harm reduction cigarette) is based on the principle of hookah smoking under its modern form whereby the tobacco rod (containing glycerol) is heated by a carbon tip instead of being burned as in a classical cigarette. The levels of numerous toxic chemicals are cut down to a great extent and the researchers found that ‘‘consistent with an earlier tobacco heating cigarette study, the vapour phase radical yields were 97% less than in a standard reference light ‘‘tar”’ cigarette (1R4F) [26,27]. As a conclusion for this review of harm reduction hypotheses, it appears that the main problem identified so far in relation to hookah smoking under its modern form is carbon monoxide [9,28]. Indeed, smoking patterns have changed a lot and smoking too often occurs in ill-ventilated places where, not less frequently, a new kind of charcoal (quick-lighting and non natural) is used as a heating source. Possibilities to reduce the emissions of such a gas within a broad harm reduction framework should have become a public health priority for 10 years now [9]. K&S have usefully blazed this harm reduction trail [6].
References [1] Funck-Brentano C, Raphael M, Lafontaine M, Arnould JP, Verstuyft C, Lebota M, et al. Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of tobacco exposure and toxicity. Lung Cancer 2006;54:11–8. [2] Sajid KM, Chaouachi K, Mahmood R. Hookah smoking and cancer. Carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers. Harm Reduction J 2008;24(5):19. Available from: http://www. harmreductionjournal.com/content/pdf/1477-7517-5-19.pdf. [3] Rodu B, Phillips CV. Switching to smokeless tobacco as a smoking cessation method: evidence from the 2000 National Health Interview Survey. Harm Reduct J 2008;23(5):18. Available from: http://www. harmreductionjournal.com/content/5/1/18. [4] Wynder EL, Hoffmann D. Reduction of tumorigenicity of cigarette smoke: an experimental approach. JAMA 1965;192:88–94. [5] Marks J. Drug misuse and social cost. Brit J Hosp Med 1994;52(2–3):65–7. [6] Kurien BT, Scofield RH. Bubbling hookah smoke through heat-solubilized curcumin/turmeric and incorporation of the curry spice as an additive or filter in cigarettes to minimize tobacco smoke-related toxicants. Med Hypotheses; 2009 [ahead of print]. Available form: http://dx.doi.org/10.1016/j.mehy. 2009.04.005. [7] Shafagoj YA, Mohammed FI, Hadidi KA. Hubble–Bubble (water pipe) smoking: levels of nicotine and cotinine in plasma, saliva and urine. Int J Clin Pharmacol Ther 2002;40(6):249–55. [8] Salameh P, Waked M, Aoun Z. Water pipe smoking: construction and validation of the Lebanon water pipe dependence scale (lwds-11). Nicotine Tob Res 2008;10:149–58. [9] Chaouachi K. Hookah (Shisha, Narghile) smoking and environmental tobacco smoke (ETS). A critical review of the relevant literature and the public health consequences. Int J Environ Res Public Health 2009;6:798–843. Available from: http://www.mdpi.com/1660-4601/6/2/798/. [10] Pakhale SS, Maru GB. Distribution of major and minor alkaloids in tobacco, mainstream and sidestream smoke of popular Indian smoking products. Food Chem Toxicol 1998;36:1131–8. [11] Pakhale SS, Jayant K, Bhide SV. Methods of reduction of harmful constituents in bidi smoke. Indian J Chest Dis Allied Sci 1985;27(3):148–52. [12] Wynder EL, Tobacco D. Tobacco and tobacco smoke. Studies in experimental carcinogenesis. New York and London: Academic Press; 1967. pp. 186, 329–330. [13] Sanghvi LD. Cancer epidemiology: the Indian scene. J Cancer Res Clin Oncol 1981;99:1–14. [14] Guillerm R, Badré R, Vignon B. Effet inhibiteurs de la fumée de tabac sur l’activité ciliaire de l’épithélium respiratoire et nature des composants responsables [inhibitory effects of tobacco smoke on the respiratory epithelium ciliary activity]. Acad Natl Med 1961(13):416–23. [15] Roffo AH. Sobre los filtros en el tabaquismo: el narguile y el algodon como filtro del alquitran de tabaco [tobacco use and filters: narghile and cotton as filters of tobacco tar]. Boletin del instituto de medicina experimental para el estudio y tratamiento del cancer 1939;16(51):255–68. [16] Rakower J, Fatal B. Study of narghile smoking in relation to cancer of the lung. Brit J Cancer 1962;16(Mar):1–6.
[17] Bhonsle RB, Murti PR, Gupta PC. Tobacco habits in India. In: Gupta PC, Hamner JE, Murti PR, editors. Control of tobacco-related cancers and other diseases. International symposium 1990. Bombay: Oxford University Press; 1992. p. 25–46. [18] Gori G. Less hazardous cigarettes – The case for hastening their regulation and promotion. Tob Rep 2004(June):30–4. [19] Sutherland G, Russell MA, Stapleton JA, Feyerabend C. Glycerol particle cigarettes: a less harmful option for chronic smokers. Thorax 1993;48(4):385–7. [20] Maziak W. The waterpipe: time for action. Addiction 2008;103(11):1763–7. [21] Maziak W, Rastam S, Ibrahim I, Ward KD, Eissenberg T. Waterpipe-associated particulate matter emissions. Nicotine Tob Res 2008;10(3):519–23. [22] ASH (action on smoking and health). Shisha 200 times worse than a cigarette say Middle East experts. Prepared by Martin Dockrell. Based on an interview with Wasim Maziak and Alan Shihadeh. [accessed 13.06.08]. [23] El-Aasar AM, El-Merzabani MM. Studies on Jurak smoke. I. The organic constitutents of Jurak smoke. J King Abdulaziz Univ (Sci) 1991;3:169–81. [24] Thielen A, Klus H, Müller L. Tobacco smoke: unraveling a controversial subject. Exp Toxicol Pathol 2008;60(2-3):141–56. [25] Zaga V, Gatta-vecchia E. Radicali liberi e fumo di sigaretta [free radicals and cigarette smoke]. G Ital Mal Torace 2002;56(5):375–91. [26] Pryor WA, Church DF, Evans MD, Rice WY Jr, Hayes JR. A comparison of the free radical chemistry of tobacco-burning cigarettes and cigarettes that only heat tobacco. Free Radic Biol Med 1990;8(3):275–9. [27] Borgerding MF, Bodnar JA, Chung HL, Mangan PP, Morrison CC, Risner CH, et al. Chemical and biological studies of a new cigarette that primarily heats tobacco. Part 1. Chemical composition of mainstream smoke. Food Chem Toxicol 1998;36(3):169–82. Corrected and republished in: Food Chem Toxicol 1998;36(7):169–82. [28] Bacha ZA, Salameh P, Waked M. Saliva cotinine and exhaled carbon monoxide levels in natural environment water pipe smokers. Inhal Toxicol 2007;19(9):771–7.
Kamal Chaouachi DIU Tabacologie, Universite Paris XI, 18 allée des petits bois, 78000 Versailles, France Tel.: +33 1 4928 9860; fax: +33 1 5839 3695 E-mail address: [email protected] doi:10.1016/j.mehy.2009.06.016
A proposed mechanism for the pathogenesis of multiple primary tumours The pathogenesis of many cancers including multiple primary tumours (MPT) is still not clear. In a previous contribution to this journal, a proposed mechanism was to explain the occurrence of frequently multicentric cancer [1]. This interpretation of tumourigenic mechanism is that the large pool of embryonic cells with the initial somatic mutation increases risk of developing one or more cancer lesions during their lifetime. In the patients with MPT of the parotid gland, most are histologically classified as Warthin’s tumours [2]. Multiple Warthin’s tumour seems to be similar with sporadic multiple tumours of breast or colon, which is related to the initial somatic mutant cell. During the early stages of embryogenesis of the parotid glands, many epithelial cells, are embedded within the lymphoid component [3]. The histogenesis of this tumour may result from these epithelial inclusions of certain mutant cells, the precursors of the salivary duct–acinar system. Sporadic multiple tumours of breast or colon is disease of elderly, suggesting that it takes time to complete all mutations in a single cell that becomes the initial cancer cell [1]. This concept can be applied to the multiple occurrence of Warthin’s tumour which also occurs most frequently in older individuals [4]. The hypothetical initial somatic mutation would be found by its presence in independent cancer lesions and in some areas of adjacent salivary gland tissue. DNA in MPT and adjacent normal sali-
Correspondence / Medical Hypotheses 73 (2009) 623–631
vary gland tissue could be checked for mutations, the histogenesis of these tumours may be resolved at the cytogenetical and molecular levels. References [1] Kurbel S, Kovacic D, Misevic T, Kovacic B. Breast or colon cancer patients with more than one tumor: are tumor and adjacent normal tissue sharing same mutations? Med Hypoth 2006;66(3):676–7. [2] Zeebregts CJ, Mastboom WJB, Noort GV, Det RJV. Synchronous tumours of the unilateral parotid gland: rare or undetected? J Cranio-Maxillofac Surg 2003;31(1):62–6. [3] Yu GY, Ma DQ, Zhang Y, et al. Multiple primary tumours of the parotid gland. Int J Oral Maxillofac Surg 2004;33(6):531–4. [4] Araki Y, Sakaguchi R. Synchronous oncocytoma and Warthin’s tumor in the ipsilateral parotid gland. Auris Nasus Larynx 2004;31(1):73–8.
Huawei He Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China Tel.: +86 10 67099211 E-mail address: [email protected] Damin Zhao Meiyan Liu Zhixiu He West China College of Stomatology, Sichuan University, Chengdu 610041, China doi:10.1016/j.mehy.2009.06.042
Can gossypol be a hope for transsexual patients (male to female) before sex reassignment surgery? Just for adjusting the body to mind Transsexualism is a sexual identity disorder distinguished by the extreme conviction of belonging to the opposite sex with a total disharmony in the original sex. Cross-sex hormonal treatment is desired by such patients to live as a member of their identified gender [1]. Endocrine treatment provides some relief from dichotomy between body habitus and gender. There are some medical risks of sex steroids. In that case, medical providers are faced with the difficult dilemma of balancing medical risks and the psychological needs of patients. Hormonal treatment has two aims: (1) to reduce the hormonally induced secondary sex characteristics of the original sex and (2) to induce the secondary sex characteristics of the new sex. Estrogen is the cornerstone for feminization of male to female (MTF) transsexual people. As cross-sex hormone therapy, estrogen is two to three times as high as the recommended doses for hormone replacement therapy in postmenopausal women [1]. Concurrent administration of hormone modulators may potentiate the effects of estrogen. Antiandrogen is theorized to lower serum levels of testosterone, thereby decreasing masculine secondary sex characteristics. Several studies reported lowering of testosterone with cyproterone acetate. This can be particularly helpful in patients with comorbidities that prohibit high levels of estrogen. Adverse effects of sex steroid therapy are apparent. There is 20fold increase in venous thrombosis [2]. Another common phenomenon is an increase in prolactin levels [3]. Depression is increased in comparison to general population [4]. Considering contraindications and potential complications, each patient must be selected
625
carefully. The endocrinological follow-up is essential and necessary. There is risk of hormone-related malignancy in transsexuals receiving treatment with cross-sex hormones [5]. There are two reports of MTF transsexuals who developed breast carcinomas while receiving estrogen treatment [6]. Several cases of lactotroph adenoma (prolactinoma) following high dose estrogen administration have been reported in patients with normal prolactin secretion before therapy [7]. Three cases of prostate cancer in MTF taking estrogen have been reported [8,9]. Gossypol is a natural polyphenolic, lipid soluble compound extracted from cotton plant (Gossypium species). Recently, it was identified as a toxin when used as an animal feed and has long been recognized as a contraceptive agent in rural areas of China with negligible toxicity profile. Later, it was discovered as potent inhibitor of Bcl-2 protein in particulary prostate cancer, regarding as a new hope for treatment of hormone independent prostate cancer [10]. In the nature, gossypol occurs in two enantiomeric forms, and ( )/( ) form of gossypol is more potent than racemic [(+)/( ) form of gossypol] form by means of antifertile action [11]. Gossypol inhibits steroidogenesis in bovine luteal cells and may have clinical application in steroid synthesis [12]. The inhibitory effect of gossypol on particulary androgen synthesis has already made gossypol a potential new drug for metastatic prostate cancer. The exact mechanism of gossypol as an inhibitor of androgen synthesis is not yet clear. However, a very recent study by Hu et al. had already demonstrated that both racemic and ( )/( ) form of gossypol potently inhibit 3b-hydroxysteroid dehydrogenase (3bHSD) and 17b-hydroxysteroid dehydrogenase 3 (17b-HSD3) synthesis in human and rat testes [11]. We hypothesised here that gossypol can be a candidate for treatment of MTF transsexualism before sex reassignment surgery. High dose estrogen therapy has some adverse effects and should not be used in some situations which are thromboembolism, cerebrovascular disease as mentioned above. Therefore, gossypol can be used alone or together with low dose of estrogen in MTF transsexual patients via the inhibitory effects on 3b-HSD and 17b-HSD3 enzymes. Further studies related to gossypol as far as steroid biosynthesis is concerned will enlighten this issue. We suppose that gossypol can be a new therapeutic agent in treatment of transsexual patients who are living in a wrong body.
References [1] Moore E, Wisniewski A, Dobs A. Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects. J Clin Endocrinol Metab 2003;88:3467–73. [2] Van Kesteren P, Asscheman H, Megens J, et al. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997;47:337–42. [3] Asscheman H, Gooren L, Assies J, et al. Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexual people. Clin Endocrinol (Oxf) 1988;28:583–8. [4] Asscheman H, Gooren L, Eklund P. Mortality and morbidity in transsexual patients with cross-gender hormone treatment. Metabolism 1989;38:869–73. [5] Mueller A, Gooren L. Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 2008;159:197–202. [6] Ganly I, Taylor EW. Breast cancer in a transsexual man receiving hormone replacement therapy. Brit J Surg 1995;82:341. [7] Kovacs K, Stefaneanu L, Ezzat S, et al. Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration. A morphologic study. Archiv Pathol Lab Med 1994;118:562–5. [8] Dorff TB, Shazer RL, Nepomuceno EM, et al. Successful treatment of metastatic androgen-independent prostate carcinoma in a transsexual patient. Clin Genitourin Cancer 2007;5:344–6. [9] Thurston AV. Carcinoma of the prostate in a trranssexual. Brit J Urol 1994;73:217.
Correspondence / Medical Hypotheses 73 (2009) 623–631
hookah might act as an anti-oxidant against a category of short half-life free radicals [25]. On the other hand, scientists have calculated the reduction rate of free radicals in a cigarette that primarily heats tobacco. Interestingly, this product (Eclipse harm reduction cigarette) is based on the principle of hookah smoking under its modern form whereby the tobacco rod (containing glycerol) is heated by a carbon tip instead of being burned as in a classical cigarette. The levels of numerous toxic chemicals are cut down to a great extent and the researchers found that ‘‘consistent with an earlier tobacco heating cigarette study, the vapour phase radical yields were 97% less than in a standard reference light ‘‘tar”’ cigarette (1R4F) [26,27]. As a conclusion for this review of harm reduction hypotheses, it appears that the main problem identified so far in relation to hookah smoking under its modern form is carbon monoxide [9,28]. Indeed, smoking patterns have changed a lot and smoking too often occurs in ill-ventilated places where, not less frequently, a new kind of charcoal (quick-lighting and non natural) is used as a heating source. Possibilities to reduce the emissions of such a gas within a broad harm reduction framework should have become a public health priority for 10 years now [9]. K&S have usefully blazed this harm reduction trail [6].
References [1] Funck-Brentano C, Raphael M, Lafontaine M, Arnould JP, Verstuyft C, Lebota M, et al. Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of tobacco exposure and toxicity. Lung Cancer 2006;54:11–8. [2] Sajid KM, Chaouachi K, Mahmood R. Hookah smoking and cancer. Carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers. Harm Reduction J 2008;24(5):19. Available from: http://www. harmreductionjournal.com/content/pdf/1477-7517-5-19.pdf. [3] Rodu B, Phillips CV. Switching to smokeless tobacco as a smoking cessation method: evidence from the 2000 National Health Interview Survey. Harm Reduct J 2008;23(5):18. Available from: http://www. harmreductionjournal.com/content/5/1/18. [4] Wynder EL, Hoffmann D. Reduction of tumorigenicity of cigarette smoke: an experimental approach. JAMA 1965;192:88–94. [5] Marks J. Drug misuse and social cost. Brit J Hosp Med 1994;52(2–3):65–7. [6] Kurien BT, Scofield RH. Bubbling hookah smoke through heat-solubilized curcumin/turmeric and incorporation of the curry spice as an additive or filter in cigarettes to minimize tobacco smoke-related toxicants. Med Hypotheses; 2009 [ahead of print]. Available form: http://dx.doi.org/10.1016/j.mehy. 2009.04.005. [7] Shafagoj YA, Mohammed FI, Hadidi KA. Hubble–Bubble (water pipe) smoking: levels of nicotine and cotinine in plasma, saliva and urine. Int J Clin Pharmacol Ther 2002;40(6):249–55. [8] Salameh P, Waked M, Aoun Z. Water pipe smoking: construction and validation of the Lebanon water pipe dependence scale (lwds-11). Nicotine Tob Res 2008;10:149–58. [9] Chaouachi K. Hookah (Shisha, Narghile) smoking and environmental tobacco smoke (ETS). A critical review of the relevant literature and the public health consequences. Int J Environ Res Public Health 2009;6:798–843. Available from: http://www.mdpi.com/1660-4601/6/2/798/. [10] Pakhale SS, Maru GB. Distribution of major and minor alkaloids in tobacco, mainstream and sidestream smoke of popular Indian smoking products. Food Chem Toxicol 1998;36:1131–8. [11] Pakhale SS, Jayant K, Bhide SV. Methods of reduction of harmful constituents in bidi smoke. Indian J Chest Dis Allied Sci 1985;27(3):148–52. [12] Wynder EL, Tobacco D. Tobacco and tobacco smoke. Studies in experimental carcinogenesis. New York and London: Academic Press; 1967. pp. 186, 329–330. [13] Sanghvi LD. Cancer epidemiology: the Indian scene. J Cancer Res Clin Oncol 1981;99:1–14. [14] Guillerm R, Badré R, Vignon B. Effet inhibiteurs de la fumée de tabac sur l’activité ciliaire de l’épithélium respiratoire et nature des composants responsables [inhibitory effects of tobacco smoke on the respiratory epithelium ciliary activity]. Acad Natl Med 1961(13):416–23. [15] Roffo AH. Sobre los filtros en el tabaquismo: el narguile y el algodon como filtro del alquitran de tabaco [tobacco use and filters: narghile and cotton as filters of tobacco tar]. Boletin del instituto de medicina experimental para el estudio y tratamiento del cancer 1939;16(51):255–68. [16] Rakower J, Fatal B. Study of narghile smoking in relation to cancer of the lung. Brit J Cancer 1962;16(Mar):1–6.
[17] Bhonsle RB, Murti PR, Gupta PC. Tobacco habits in India. In: Gupta PC, Hamner JE, Murti PR, editors. Control of tobacco-related cancers and other diseases. International symposium 1990. Bombay: Oxford University Press; 1992. p. 25–46. [18] Gori G. Less hazardous cigarettes – The case for hastening their regulation and promotion. Tob Rep 2004(June):30–4. [19] Sutherland G, Russell MA, Stapleton JA, Feyerabend C. Glycerol particle cigarettes: a less harmful option for chronic smokers. Thorax 1993;48(4):385–7. [20] Maziak W. The waterpipe: time for action. Addiction 2008;103(11):1763–7. [21] Maziak W, Rastam S, Ibrahim I, Ward KD, Eissenberg T. Waterpipe-associated particulate matter emissions. Nicotine Tob Res 2008;10(3):519–23. [22] ASH (action on smoking and health). Shisha 200 times worse than a cigarette say Middle East experts. Prepared by Martin Dockrell. Based on an interview with Wasim Maziak and Alan Shihadeh.
Kamal Chaouachi DIU Tabacologie, Universite Paris XI, 18 allée des petits bois, 78000 Versailles, France Tel.: +33 1 4928 9860; fax: +33 1 5839 3695 E-mail address: [email protected] doi:10.1016/j.mehy.2009.06.016
A proposed mechanism for the pathogenesis of multiple primary tumours The pathogenesis of many cancers including multiple primary tumours (MPT) is still not clear. In a previous contribution to this journal, a proposed mechanism was to explain the occurrence of frequently multicentric cancer [1]. This interpretation of tumourigenic mechanism is that the large pool of embryonic cells with the initial somatic mutation increases risk of developing one or more cancer lesions during their lifetime. In the patients with MPT of the parotid gland, most are histologically classified as Warthin’s tumours [2]. Multiple Warthin’s tumour seems to be similar with sporadic multiple tumours of breast or colon, which is related to the initial somatic mutant cell. During the early stages of embryogenesis of the parotid glands, many epithelial cells, are embedded within the lymphoid component [3]. The histogenesis of this tumour may result from these epithelial inclusions of certain mutant cells, the precursors of the salivary duct–acinar system. Sporadic multiple tumours of breast or colon is disease of elderly, suggesting that it takes time to complete all mutations in a single cell that becomes the initial cancer cell [1]. This concept can be applied to the multiple occurrence of Warthin’s tumour which also occurs most frequently in older individuals [4]. The hypothetical initial somatic mutation would be found by its presence in independent cancer lesions and in some areas of adjacent salivary gland tissue. DNA in MPT and adjacent normal sali-
Correspondence / Medical Hypotheses 73 (2009) 623–631
vary gland tissue could be checked for mutations, the histogenesis of these tumours may be resolved at the cytogenetical and molecular levels. References [1] Kurbel S, Kovacic D, Misevic T, Kovacic B. Breast or colon cancer patients with more than one tumor: are tumor and adjacent normal tissue sharing same mutations? Med Hypoth 2006;66(3):676–7. [2] Zeebregts CJ, Mastboom WJB, Noort GV, Det RJV. Synchronous tumours of the unilateral parotid gland: rare or undetected? J Cranio-Maxillofac Surg 2003;31(1):62–6. [3] Yu GY, Ma DQ, Zhang Y, et al. Multiple primary tumours of the parotid gland. Int J Oral Maxillofac Surg 2004;33(6):531–4. [4] Araki Y, Sakaguchi R. Synchronous oncocytoma and Warthin’s tumor in the ipsilateral parotid gland. Auris Nasus Larynx 2004;31(1):73–8.
Huawei He Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China Tel.: +86 10 67099211 E-mail address: [email protected] Damin Zhao Meiyan Liu Zhixiu He West China College of Stomatology, Sichuan University, Chengdu 610041, China doi:10.1016/j.mehy.2009.06.042
Can gossypol be a hope for transsexual patients (male to female) before sex reassignment surgery? Just for adjusting the body to mind Transsexualism is a sexual identity disorder distinguished by the extreme conviction of belonging to the opposite sex with a total disharmony in the original sex. Cross-sex hormonal treatment is desired by such patients to live as a member of their identified gender [1]. Endocrine treatment provides some relief from dichotomy between body habitus and gender. There are some medical risks of sex steroids. In that case, medical providers are faced with the difficult dilemma of balancing medical risks and the psychological needs of patients. Hormonal treatment has two aims: (1) to reduce the hormonally induced secondary sex characteristics of the original sex and (2) to induce the secondary sex characteristics of the new sex. Estrogen is the cornerstone for feminization of male to female (MTF) transsexual people. As cross-sex hormone therapy, estrogen is two to three times as high as the recommended doses for hormone replacement therapy in postmenopausal women [1]. Concurrent administration of hormone modulators may potentiate the effects of estrogen. Antiandrogen is theorized to lower serum levels of testosterone, thereby decreasing masculine secondary sex characteristics. Several studies reported lowering of testosterone with cyproterone acetate. This can be particularly helpful in patients with comorbidities that prohibit high levels of estrogen. Adverse effects of sex steroid therapy are apparent. There is 20fold increase in venous thrombosis [2]. Another common phenomenon is an increase in prolactin levels [3]. Depression is increased in comparison to general population [4]. Considering contraindications and potential complications, each patient must be selected
625
carefully. The endocrinological follow-up is essential and necessary. There is risk of hormone-related malignancy in transsexuals receiving treatment with cross-sex hormones [5]. There are two reports of MTF transsexuals who developed breast carcinomas while receiving estrogen treatment [6]. Several cases of lactotroph adenoma (prolactinoma) following high dose estrogen administration have been reported in patients with normal prolactin secretion before therapy [7]. Three cases of prostate cancer in MTF taking estrogen have been reported [8,9]. Gossypol is a natural polyphenolic, lipid soluble compound extracted from cotton plant (Gossypium species). Recently, it was identified as a toxin when used as an animal feed and has long been recognized as a contraceptive agent in rural areas of China with negligible toxicity profile. Later, it was discovered as potent inhibitor of Bcl-2 protein in particulary prostate cancer, regarding as a new hope for treatment of hormone independent prostate cancer [10]. In the nature, gossypol occurs in two enantiomeric forms, and ( )/( ) form of gossypol is more potent than racemic [(+)/( ) form of gossypol] form by means of antifertile action [11]. Gossypol inhibits steroidogenesis in bovine luteal cells and may have clinical application in steroid synthesis [12]. The inhibitory effect of gossypol on particulary androgen synthesis has already made gossypol a potential new drug for metastatic prostate cancer. The exact mechanism of gossypol as an inhibitor of androgen synthesis is not yet clear. However, a very recent study by Hu et al. had already demonstrated that both racemic and ( )/( ) form of gossypol potently inhibit 3b-hydroxysteroid dehydrogenase (3bHSD) and 17b-hydroxysteroid dehydrogenase 3 (17b-HSD3) synthesis in human and rat testes [11]. We hypothesised here that gossypol can be a candidate for treatment of MTF transsexualism before sex reassignment surgery. High dose estrogen therapy has some adverse effects and should not be used in some situations which are thromboembolism, cerebrovascular disease as mentioned above. Therefore, gossypol can be used alone or together with low dose of estrogen in MTF transsexual patients via the inhibitory effects on 3b-HSD and 17b-HSD3 enzymes. Further studies related to gossypol as far as steroid biosynthesis is concerned will enlighten this issue. We suppose that gossypol can be a new therapeutic agent in treatment of transsexual patients who are living in a wrong body.
References [1] Moore E, Wisniewski A, Dobs A. Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects. J Clin Endocrinol Metab 2003;88:3467–73. [2] Van Kesteren P, Asscheman H, Megens J, et al. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997;47:337–42. [3] Asscheman H, Gooren L, Assies J, et al. Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexual people. Clin Endocrinol (Oxf) 1988;28:583–8. [4] Asscheman H, Gooren L, Eklund P. Mortality and morbidity in transsexual patients with cross-gender hormone treatment. Metabolism 1989;38:869–73. [5] Mueller A, Gooren L. Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 2008;159:197–202. [6] Ganly I, Taylor EW. Breast cancer in a transsexual man receiving hormone replacement therapy. Brit J Surg 1995;82:341. [7] Kovacs K, Stefaneanu L, Ezzat S, et al. Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration. A morphologic study. Archiv Pathol Lab Med 1994;118:562–5. [8] Dorff TB, Shazer RL, Nepomuceno EM, et al. Successful treatment of metastatic androgen-independent prostate carcinoma in a transsexual patient. Clin Genitourin Cancer 2007;5:344–6. [9] Thurston AV. Carcinoma of the prostate in a trranssexual. Brit J Urol 1994;73:217.