AussieThunder said:
I've read that too, but I think it is bullshit. I'll know for sure when I repeat my experiment, but at this point i'm confident that topical spironolactone lowers the blood levels of total and free testosterone.
While topical spirolactone seems to have no systemic effect in men (1) during short term treatment, maybe it does during medium-long term treatment
Regarding Deepglute's observations, while my understanding was also that spirolactone is simply a androgen receptor blocker, oral spirolactone does seem to decrease testosterone levels in men (5, 6, 7, 8, 9),, even though these studies done in women and men contradict these findings (2,3,4,10)
How long were you using spirolactone and what were the other ingredients in the topical formulation?
1-Lack of endocrine systemic side effects after topical application of spironolactone in man.
Rey FO, Valterio C, Locatelli L, Ramelet AA, Felber JP.
Departement de Medecine, C.H.U.V., Lausanne, Switzerland.
In six healthy male volunteers, the percutaneous absorption of spironolactone was compared with placebo in a double-blind crossover study. The subjects were randomly given either a cream containing 5% spironolactone or placebo to be applied in a randomized sequential way to a well defined skin area equivalent to 55% of body area. During the 72 h following the application of the ointment, blood levels of canrenone, the major metabolite of spironolactone, have been determined. In order to estimate the systemic antiandrogenic effect of spironolactone, plasma levels of 17-alpha-Hydroxy progesterone (17 alpha-OH-P), Testosterone (pT) and non-conjugated 3 alpha-Androstanediol (3 alpha-diol, metabolite of the active androgen 5 alpha-Dihydrotestosterone or DHT) as well as salivary Testosterone (sT) which relate to the free and active plasma testosterone fraction have also been measured. Urinary levels of canrenone have been determined 48 hours after cream application. No changes in any levels of these hormones have been detected and plasma canrenone levels were undetectable during the 72 hours of topical treatment. Topically administered, spironolactone appears to have only a local skin impregnation.
2-Comparison of the efficiency of anti-androgenic regimens consisting of spironolactone, Diane 35, and cyproterone acetate in hirsutism.
Sert M, Tetiker T, Kirim S.
Department of Internal Medicine, Division of Endocrinology, Cukurova University Medical School, Adana, Turkey.
muratser@mail.cu.edu.tr
The aim of the present study was to evaluate the effects of three different anti-androgenic drug-therapy regimens, Diane 35 (cyproterone acetate (CPA) [2 mg] and ethinyl estradiol [35 microg]) plus CPA, Diane 35 plus spironolactone, and spironolactone alone, in patients with hirsutism. In this prospective, randomized clinical study, 79 subjects with idiopathic hirsutismus were studied. The patients were divided into 3 groups. Group I patients (n=32) were treated with Diane 35 plus CPA, group II patients (n=25) with Diane 35 plus spironolactone [100 mg], and group III patients (n=22) with spironolactone [100 mg] alone. Serum FSH, LH, testosterone (T), and DHEAS levels were analyzed before and after treatment at 6 and 12 months. Hirsutism scores were graded according to the Ferriman-Gallwey scoring system, and side effects were monitored. All treatment regimens were found to be efficient and well-tolerated, and none of the patients stopped therapy due to any adverse event. However, in hormone screening, only patients on the Diane 35 plus CPA regimen revealed a decrease in serum T levels after therapy. As such, treatment of each hirsute patient should be planned individually, but with regard to both cost-efficiency and potential side effects, we recommend spironolactone alone in the treatment of hirsutismus.
3 - [Serum hormones before and during therapy with cyproterone acetate and spironolactone in patients with androgenization]
[Article in German]
Grunwald K, Rabe T, Schlereth G, Runnebaum B.
Abt. fur gynakologische Endokrinologie und Fortpflanzungsmedizin, Universitats-Frauenklinik Heidelberg.
The effect of cyproterone acetate (CPA) and spironolactone (SPL) on the serum androgen concentrations of premenopausal women with symptoms of hyperandrogenism were investigated in a total of 39 women. The observation period was 12 months. CPA was administered according to the Hammerstein regimen: cyproterone acetate (CPA) [Androcur] 100 mg/die 5.-14. day of the cycle; ethinylestradiol (EE) [Progynon C]: 40 mg/die 5.-25. day of the cycle; Spironolactone (SPL) was given in a dosage of 100 mg/die from day 1.-21. of the cycle. During the therapy with CPA a significant decrease of total testosterone (61%), free testosterone (78%), LH (48%) and 17 alpha-Hydroxyprogesterone (72%) was observed; during the medication with spironolacton only a significant decrease of 5 alpha-dihydrotestosterone (81%), which could not be seen during CPA use, was observed. Serum concentrations of total testosterone, free testosterone, LH and 17 alpha-Hydroxyprogesterone remained unchanged. DHA and DHAS did not change during neither medication. Since peripheral androgens were not suppressed by SPL the positive therapeutical effect of SPL can be explained by the antiandrogenic effect at the level of the receptor. A disadvantage of spironolacton is the lack of contraceptive efficacy. In cases where contraindication for oral contraceptives are present SPL can be considered as a good alternative to CPA. The suppressive effect of CPA/EE on total testosterone, LH addition to the antivulatory effect makes it the preferable medication for hyperandrogenemic patients with polycystic changes of the ovaries (PCOD).
4 - Oral spironolactone therapy in male patients with rosacea.
Aizawa H, Niimura M.
Department of Dermatology, Jikei University School of Medicine, Tokyo, Japan.
Spironolactone at 50 mg/day was orally administered for four weeks to 13 male patients with rosacea in order to observe its clinical effectiveness. Serum estradiol (E2), 17OH-progesterone (17OH-P4), testosterone (T), androstenedione (delta 4 A), dihydrotestosterone (DHT), dehydro-epiandrosterone sulfate (DHEA-S) were measured prior to and after treatment. Although there were no significant changes in T, delta 4A, DHT, or DHEA-S, the serum levels of 17OH-P4 increased significantly. E2 tended to increase, although the change was not significant. Two of the 13 patients discontinued spironolactone treatment because of general malaise, but seven of the remaining eleven patients exhibited an improvement in their rosacea. These findings demonstrate that a low dose of spironolactone is effective in the treatment of rosacea in some male patients and suggest that it is possible that changes in the metabolism of sex steroid hormones such as cytochrome p-450 isozymes have some bearing on the etiology of rosacea.
5 - Spironolactone and cimetidine in treatment of acne.
Hatwal A, Bhatt RP, Agrawal JK, Singh G, Bajpai HS.
Department of Medicine, Banaras Hindu University, Varanasi, India.
In an open therapeutic trial, 50 patients with acne vulgaris were randomly allocated to one of two groups. One group received spironolactone 100 mg daily and the other cimetidine 1.6 g daily for 12 weeks. Clinical severity of acne and sebum excretion decreased significantly at the end of the trial with both drugs, but significantly more with spironolactone. Mean serum levels of testosterone, androstenedione and dehydroepiandrosterone-sulfate decreased significantly with spironolactone but showed no change with cimetidine. Our data suggest that spironolactone may be useful as antiandrogen in the short term therapy of acne vulgaris.
6 -
[The influence of spironolactone on the concentration of gonadotrophins and gonadal hormones in prostatic hypertrophy (author's transl)]
[Article in French]
Zgliczynski S, Baranowska B, Szymanowski J.
The authors examined the influence of spironolactone on the concentration of testosterone, 5 alpha - dihydrotestosterone (DHT), progesterone, oestradiol (E2), LH, and FSH in 47 patients with prostatic hypertrophy, aged from 60 to 80 years. The control group consisted of 58 men of the same age. Spironolactone was prescribed at a dose of 100 mg per day for three months. There was a considerable fall in the concentration of testosterone and of DHT and, at the same time, an increase in the concentration of progesterone, E2 and LH. After treatment with spironolactone there was a decrease in the size of the prostate gland. Results obtained show that spironolactone is an effective drug in the treatment of prostatic hypertrophy, since it inhibits androgen metabolism
7 - Pathophysiology of spironolactone-induced gynecomastia.
Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH.
Peripheral blood levels of testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone and the metabolic clearance rates of testosterone and estradiol, as well as the peripheral conversion of testosterone into estradiol, were measured in 16 patients with hypertension. Six of these patients were treated with spironolactone and developed gynecomastia. The other 10 patients served as control subjects. The blood testosterone level in the spironolactone-treated group (2.7 +/- 0.5 ng/ml) was significantly less (P less than 0.02) than in the control group (4.4 +/- 0.4 ng/ml). On the other hand, blood estradiol levels in the spironolactone group (30 +/- 4 pg/ml) were significantly greater (P less than 0.01) than in the control group (13 +/- 2 pg/ml). These changes were primarily due to significant increases in the metabolic clearance rate of testosterone (P less than 0.02) and in the rate of peripheral conversion of testosterone into estradiol (P less than 0.001) in the spironolactone-treated group. Thus, spironolactone does alter the peripheral metabolism of testosterone resulting in changes in the ratio of testosterone to estradiol, which could contribute to the production of gynecomastia.
8- Spironolactone and endocrine dysfunction.
[No authors listed]
Therapy with spironolactone is often associated with estrogenlike side-effects, including impotence and gynecomastia in men and menstrual irregularity in women. Several possible mechanisms by which spironolactone could cause these side-effects have been identified. Spironolactone has been shown to affect both gonadal and adrenal steroidogenesis, to elevate plasma gonadotrophin levels in children, and to act as an antiandrogen at the target tissue level. This conference presents a discussion of how these effects might interact to produce the endocrine side effects associated with spironolactone therapy.
9 -
[Sexual side-effects of spironolactones. Possible mechanisms of their anti-androgen action]
[Article in French]
Corvol P, Mahoudeau JA, Valcke JC, Menard J, Bricaire H.
Spirolactones (spironolactone, potassium canrenoate) may produce secundary sexual effects such as gynecomastia in man and menstrual disturbances in women. The mechanism of action of the antiandrogenic effects has been studied in man and rat. Acute i.v. injection of potassium canrenoate into man results in a decrease of plasma testosterone, without any change of gonadotropins. This decrease might be due to an impaired testicular steroidogenesis. On the other hand, spirolactones have an antiandrogenic effect at the target cells level. They do not modify the prostate 5alpha-reductase activity; however, they do inhibit the binding of androgens to their receptors. Thus the spirolactones interact with both biosynthesis and peripheral action of androgens.
10 -Effect of spironolactone on sex hormones in man.
Stripp B, Taylor AA, Bartter FC, Gillette JR, Loriaux DL, Easley R, Menard RH.
Administration spironolactone at a dosage of 400 mg/day to healthy male volunteers for 5 days resulted in a significant rise in plasma progesterone and 17alpha-hydroxyprogesterone which persisted throughout the study. A transient increase in plasma FSH and LH concentration was observed after the second but not the third or fifth days of drug administration. There was no change in plasma concentration of testosterone, 17beta-estradiol, or prolactin. These findings are consistent with a previously-reported spironolactone-induced destruction of the microsomal enzyme cytochrome P-450, an enzyme necessary for 17-hydroxylase and desmolase activity. The results do not explain the decrease of libido, the impotence, and the gynecomastia frequently associated with spironolactone therapy in males.
