QuoteCan gossypol be a hope for transsexualpatients (male to female) before sex reassignment surgery? Just for adjusting the body to mind?
Received 12 June 2009;
accepted 24 June 2009.
Available online 3 August 2009.
Article Outline
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 20-fold 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 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] I. Ganly and E.W. Taylor, Breast cancer in a transsexual man receiving hormone replacement therapy, Brit J Surg 82 (1995), p. 341.
[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] and [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 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase 3 (17β-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 3β-HSD and 17β-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.
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