• Leo Rex

Masteron: Master of None

Updated: Nov 7

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If there ever were any studies indicating drostanolone’s affinity or efficacy for steroid receptors, they are not accessible online and likely predate the 1970’s. To properly understand the pharmacodynamics of the molecule, one would need to take blood samples across a period of time to analyze the proportion of metabolites present. Then, the major metabolites would need to be tested on human recombinant steroid hormone receptors (as well as other things, e.g. to see if it is a substrate for aromatase), including their response elements, to give a picture of what is happening.


PHARMACOKINETICS


1. Masteron (drostanolone – 2alpha-methyl-17beta-hydroxy-5alpha-androstan-3-one) and Proviron (mesterolone – 1alpha-methyl-17beta-hydroxy-5alpha-androstan-2-one) are methyl-5alpha-dihydrotestosterones. The major metabolite of Proviron in human urine is 1alpha-methyl-androsterone and the major metabolite of Masteron is 2alpha-methyl-androsterone[1].

a. For reference, dihydrotestosterone is 5alpha-androstanolone. Androsterone is a neurosteroid with a weak androgenic effect, called 3alpha-hydroxy-5alpha-androstan-17-one.

2. A sulfated metabolite (2alpha-methyl-5alpha-androstan-17-one-2beta-ol-3alpha-sulfate) and a glucuronide-conjugated metabolite (2alpha-methyl-5alpha-androstan-17-one-3alpha-O-glucuronide) are present in human urine up to 24 days after a single injection of drostanolone (without an ester)[2].

3. The metabolite used for doping control is hydrolyzed and detectable for up to 29 days. There is also a non-hydrolysed sulfated version of the main drostanolone metabolite (3alpha-hydroxy-2alpha-methyl-5alpha-androstan-17-one) which is detectable for up to 25 days[3].

4. Fungi carry P450 cytochrome enzymes. Consequently, they are used in microbial transformation studies of chemical compounds, to learn about the nature of metabolites of a parent compound. Microbial studies have recently discovered several new metabolites of drostanolone[4].

5. Drostanolone is esterified in the position of the O-H hydroxyl group to produce drostanolone propionate[5]. A graphical depiction of drostanolone as compared to drostanolone propionate can be found in this citation.

6. Superdrol (17-methyldrostanolone) can be synthesized from drostanolone as described in this citation[6].


PHARMACODYNAMICS


1. There are hormonal treatments for breast cancers in women. The recognition that many of the androgens used to treat cancerous women produced virilization led to the development of drostanolone proprionate in the 1950’s, as it was thought not to produce virilization[7].

2. It appears that drostanolone does not bind to estrogen receptors, although this research is old and understanding of estrogen receptors has progressed since its publication (the nuclear estrogen receptor beta was only discovered in 1996[8]). It does bind to the androgen receptor[9].

3. Androgens can reduce estradiol’s association to its nuclear alpha receptor, while high doses of androgens appear to activate the receptor’s nuclear translocation[10].


ANABOLIC


1. Drostanolone produced an anabolic effect in cancerous rats[11].


CANCER


1. It has been thought that[12]:

a. Drostanolone propionate reduces the uptake of 17beta-estradiol by breast cancer tumor cells.

b. Drostanolone propionate diverts reduced NADPH into a diaphorase system, thus limiting its influence on biosynthesis in the tumor.

c. Note that in the cited case report, 17 months of treatment with drostanolone propionate failed to virilize a 55-year-old premenopausal lady, though doses were not reported.

2. In clinic, drostanolone was not superior to nandrolone in producing remissions of advanced breast cancers[13].

3. In a randomized trial of women with breast cancer, a treatment including the SERM tamoxifen and drostanolone performed better than chemotherapy and better than chemotherapy plus tamoxifen and drostanolone[14].

4. Microbial studies of drostanolone enanthate, using Cephalosporium aphidicola and Fusarium lini yielded 8 metabolites (5 of which were new), which were in turn tested against cancer cell lines from the human cervix (HeLa), prostate (PC-3), lung (H460), and colon (HCT116)[15].

a. Drostanolone and metabolite 9 were more cytotoxic to the colon cancer cell line than the chemotherapeutic medication cisplatin.

b. Drostanolone and metabolites 3 and 4 were more cytotoxic against the lung cancer cell line than cisplatin.

c. The metabolites 5, 8, and 9 were more cytotoxic against the cervical cancer line than cisplatin.

d. The metabolites 3, 4, 6, 8, and 9 were more cytotoxic against the prostate cancer cell line than cisplatin.

e. The metabolites were also tested for toxicity against normal mouse cell lines. Only metabolites 8 and 9 were found to be toxic to these mouse cell lines.

5. Although drostanolone was used in the treatment of breast cancers in the 1970’s and 1980’s, even in 1998[16], it was unclear how the androgen receptor affected breast cancer cells.

a. In the early 2000’s, it was shown that androgens could inhibit some of the response elements of the alpha estrogen receptor[17].

b. More recent research indicates that in ER-, HER2+ breast tumors, androgen signaling may be oncogenic[18].

6. Also, some androgens affect estrogen receptors positively:

a. Several androgens exert effects on the alpha estrogen receptor, including DHEA[19].

b. 3B-Androstanediol, a metabolite of DHT, regulates brain function via the beta estrogen receptors[20].

[1] De Boer, D., De Jong, E. G., Maes, R. A. A., & Van Rossum, J. M. (1992). The methyl-5α-dihydrotestosterones mesterolone and drostanolone; gas chromatographic/mass spectrometric characterization of the urinary metabolites. The Journal of Steroid Biochemistry and Molecular Biology, 42(3-4), 411-419. [2] Liu, Y., Lu, J., Yang, S., Zhang, Q., & Xu, Y. (2016). New drostanolone metabolites in human urine by liquid chromatography time-of-flight tandem mass spectrometry and their application for doping control. Steroids, 108, 61-67. [3] Albertsdóttir, A. D., Van Gansbeke, W., Coppieters, G., Balgimbekova, K., Van Eenoo, P., & Polet, M. (2020). Searching for new long term urinary metabolites of metenolone and drostanolone by gas chromatography mass spectrometry with a focus on non‐hydrolysed sulfates. Drug Testing and Analysis. [4] Hussain, Z., Hussain, N., Hussain, S., & Choudhary, M. I. (2020). Seven new metabolites of drostanolone heptanoate by using Beauveria bassiana, and Macrophomina phaseolina cell suspension cultures. RSC Advances, 10(1), 451-460. [5] Borodi, G., Turza, A., & Bende, A. (2020). Exploring the Polymorphism of Drostanolone Propionate. Molecules, 25(6), 1436. [6] Ayotte, C., Goudreault, D., Cyr, D., Gauthier, J., Ayotte, P., Larochelle, C., & Poirier, D. (2006). Characterisation of chemical and pharmacological properties of new steroids related to doping of athletes. Recent advances in doping analysis, 14, 151-160. [7] BLACKBURN, C., & CHILDS, J. D. (1959, March). Use of 2 alpha-methyl androstan-17 beta-ol, 3-one (2-methyl dihydrotestosterone) in the treatment of advanced cancer of the breast. In Proceedings of the staff meetings. Mayo Clinic (Vol. 34, No. 5, pp. 113-126). [8] Kuiper, G. G., Carlsson, B. O., Grandien, K. A. J., Enmark, E., Häggblad, J., Nilsson, S., & Gustafsson, J. A. (1997). Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology, 138(3), 863-870. [9] Trams, G. (1977). Effect of drostanolone propionate on the binding of oestradiol and dihydrotestosterone by normal and malignant target tissues. European Journal of Cancer (1965), 13(2), 149-153. [10] Rochefort, H., & Garcia, M. (1976). Androgen on the estrogen receptor I—Binding and in vivo nuclear translocation. Steroids, 28(4), 549-560. [11] Mückter, H., Frankus, E., & More, E. (1970). Experimental Investigations with 1-(Morpholinomethyl)-4-phthalimidopiperidindione-2, 6 and Drostanolone Propionate in Dimethylbenzanthracene-induced Tumors of Sprague-Dawley Rats. Cancer Research, 30(2), 430-438. [12] Heney, N. M. (1970). Treatment of Advanced Breast Carcinoma with Drostanolone Propionate: A Case Report. Bristol Medico-Chirurgical Journal, 85(3), 75. [13] Wolff, G., & Rieche, K. (1978). Androgen therapy of incurable breast neoplasms. Controlled clinical study: nandrolone-testololactone-drostanolone. Onkologie, 1(4), 172-174. [14] Clavel, B., Cappelaere, J. P., Guerin, J., Klein, T., Pommatau, E., & Berlie, J. (1982). Management of advanced breast cancer in post-menopausal women. A comparative trial of hormonal therapy, chemotherapy, and a combination of both. La semaine des hopitaux: organe fonde par l'Association d'enseignement medical des hopitaux de Paris, 58(34), 1919-1923. [15] Choudhary, M. I., Siddiqui, M., Yousuf, S., Fatima, N., Ahmad, M. S., & Choudhry, H. (2017). Bio-catalytic structural transformation of anti-cancer steroid, drostanolone enanthate with Cephalosporium aphidicola and Fusarium lini, and cytotoxic potential evaluation of its metabolites against certain cancer cell lines. Frontiers in pharmacology, 8, 900. [16] Birrell, S. N., Hall, R. E., & Tilley, W. D. (1998). Role of the androgen receptor in human breast cancer. Journal of mammary gland biology and neoplasia, 3(1), 95-103. [17] Peters, A. A., Buchanan, G., Ricciardelli, C., Bianco-Miotto, T., Centenera, M. M., Harris, J. M., ... & Henshall, S. M. (2009). Androgen receptor inhibits estrogen receptor-α activity and is prognostic in breast cancer. Cancer research, 69(15), 6131-6140. [18] Ni, M., Chen, Y., Lim, E., Wimberly, H., Bailey, S. T., Imai, Y., ... & Brown, M. (2011). Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer cell, 20(1), 119-131. [19] Maggiolini, M., Donzé, O., Jeannin, E., Andò, S., & Picard, D. (1999). Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor α. Cancer research, 59(19), 4864-4869. [20] Handa, R. J., Pak, T. R., Kudwa, A. E., Lund, T. D., & Hinds, L. (2008). An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β, 17β-diol. Hormones and behavior, 53(5), 741-752.

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