Here's everything I could find on the science behind spironolactone, I've done vast amounts of research on the compound itself and the specific topical formulation before purchasing S5 cream for personal use. Enter the PMID numbers into Google to get the link to the actual study on PubMed:
Topical spironolactone inhibits DHT activity in the scalp via the same two mechanisms as ketoconazole albeit with much greater potency: androgen receptor antagonism and inhibition of the CYP17A1 enzyme as well as having three additional pharmacological mechanisms: progesterone receptor agonism which results in antigonadotropin effects, indirect estrogenic effects which increase the level of sex hormone binding globulin (SHBG binds to testosterone and hence lowers free T levels, therefore lowering the amount of free T converted to DHT) and weak 5α-reductase inhibition (these last two lesser known mechanisms of spironolactone are supported via these studies and links: PMID: 7829618, PMID: 4033118, PMCID: PMC2923944,
http://www.dermnetnz.org/treatments/antiandrogens.html
http://www.jcadonline.com/2012/03/o...ased-on-current-data-and-clinical-experience/
http://www.jcadonline.com/2009/12/hormonal-treatment-of-acne-in-women/)
This makes spironolactone the only medication indicated for androgenic alopecia that has a pharmacological profile that includes three antiandrogenic mechanisms: androgen receptor antagonism, androgen synthesis inhibition via enzyme inhibition and gonadotropin suppression.
(References for effectiveness of topical and oral spironolactone: PMID: 2972662, PMID: 20510769, PMID: 17222303,
Reference [22] on stated link:
http://www.medscape.com/viewarticle/805516_3)
There was also a post I saw on another forum by a member who I believe posts on here as well, his name's Bryan. He apparently has a hard copy of an old study done on topical spironolactone for Androgenetic Alopecia:
"Topical Spironolactone in the Treatment of Androgenetic Alopecia", R. Bianchini, G. Buzzetti, L. Colombo, Rivista Italiana di Biologia e Medicina, Vol. 6(2) (pp 129-131), 1986. 52 patients completed a year-long study in which they were treated twice daily with a 3% topical spironolactone solution in a vehicle of ethanol, water, and glycerin.
They say: "We evaluated hair density at the site treated, according to a conventional rating scale (0 = hair almost absent; 1 = hair very scanty; 2 = hair rather thin; 3 = hair moderately thin), on the basis of clinical assessment and standardized photography. These observations were carried out before, and after 6 and 12 months of treatment. The data obtained were analyzed by the Friedman and Wilcoxon tests".
From a starting score of exactly 1.00, after 6 months it was 1.212 (they claim a probability p<0.01 for this result) and after 12 months it was 1.75 (p< 0.001).
That's about it. No hair-counts, trichograms, or hair-shaft diameters; just a somewhat subjective rating of these 52 subjects. However, they do provide before-and-after photographs of a couple of them, and there *is* some interesting hair-growth that you can plainly see; it's similar to those Propecia pictures of good responders that we've all seen on Web sites.
Here are the last few comments in the study: "With S therapy, several of our patients noted regrowth of hair and its long-term administration did not produce side effects or any decrease in blood pressure. To our knowledge, use of topical S in the treatment of AA has never been reported before. In conclusion, we believe that S acts directly as an antagonist of dihydrotestosterone on target tissue. Furthermore, the present study shows the possibility of using a testosterone inhibitory drug without systemic antiandrogenic side effects".
Some more FAQs about S5 cream should be answered with the following information:
While some people are skeptical about the legitimacy of S5 cream and some even questioning its spironolactone content (a few people wondering if it even contains any spironolactone at all) all I have to say to that is that a decent trick to tell if spironolactone is present is its notorious odour. Being a drug that’s molecular structure contains a sulphur atom; it has a mercaptan-like odour, often described by many as a ‘rotten egg’ smell. I personally can confirm that S5 cream has this specific odour, although you can tell it’s been masked with limonene, resulting in a bit of a combination smell.
The vehicle used in S5 cream also comes under fire in various internet forums with many exclaiming ‘how do we know spironolactone is even absorbed at all’, this is also unfounded because the vehicle used for S5 (alcohol and triethanolamine) is the same as the vehicle used by compounding pharmacies who also make topical spironolactone formulations.
(Reference from this compounding pharmacy’s specific spironolactone formulation ID: US Pharm. 2012;37(12):43-44)
S5 Day Cream contains 1% caffeine in addition to 5% spironolactone; the addition of caffeine is thought to provide additional benefits for hair loss although further
in vivo studies are needed to prove said benefits. (Evidence from
in vitro studies showing stimulation of hair growth, suppression of androgen activity and 5α-reductase inhibition: PMID: 23075568, PMID: 24836650, PMID: 17214716)
S5 Bedtime cream contains no caffeine but instead includes 1% adenosine in addition to 5% spironolactone; the addition of adenosine is proven to provide benefits for hair loss with good evidence from studies done in humans, with results including thickening of hair density and one study even showing that topical adenosine in a 0.75% formulation was only slightly less effective than 5% minoxidil, with patients being more satisfied with the results from adenosine. (PMID: 24183218, PMID: 25925959)
It should be worth mentioning that while DHT is the pinnacle cause of androgenic alopecia, it is currently unknown whether other androgens have a pathological role. What we do know as of now is even those who are taking finasteride or even the potent dutasteride, some still inexplicably continue to lose hair and when a male with androgenic alopecia is castrated, said hair loss ceases to continue, this serves to suggest that other harmful androgens possibly have a lesser pathological role. With this in mind, androgen receptor antagonists such as ketoconazole and spironolactone offer peace of mind due to the fact that in addition to preventing DHT from binding to the androgen receptor, they also will prevent any other potentially harmful androgens from doing so as well.
As for my personal opinion, I cannot say much as of now as I've only started using S5 cream a few days ago, I have however noticed less hair on my hands in the shower and on my pillow. Hope this helps!