Androgenetic alopecia and risk of prostate cancer: A systematic review and meta-analysis.

J Am Acad Dermatol. 2013 Feb 7. pii: S0190-9622(12)02302-X. doi: 10.1016/j.jaad.2012.11.034.
Androgenetic alopecia and risk of prostate cancer: A systematic review and meta-analysis.
Amoretti A, Laydner H, Bergfeld W.
Source
Hair Center, Department of Dermatology, Cleveland Clinic, Cleveland, Ohio.

BACKGROUND:
Androgenetic alopecia (AGA) is a genetically determined skin condition strongly age dependent and androgens are assumed to play an important role in its development. A link between AGA and prostate cancer has been hypothesized because of their similar risk factors.
OBJECTIVE:
We sought to systematically review the evidence available on the association between AGA and risk of prostate cancer.
METHODS:
We searched the electronic databases MEDLINE and Cochrane for studies examining the association between AGA and risk of prostate cancer. We estimated pooled odds ratios (OR) and 95% confidence intervals. We also analyzed the OR for individual hair loss patterns, as defined by the Hamilton scale.
RESULTS:
A total of 7 case-control studies including 8994 patients-4078 cases and 4916 controls-were reviewed. One cohort study was identified but did not meet our inclusion criteria. There was statistically significant association between vertex baldness and prostate cancer (OR 1.25; 95% confidence interval 1.09-1.44; Z = 3.13; P = .002). No statistically significant association between AGA (any pattern) and prostate cancer was identified (OR 1.03; 95% confidence interval 0.93-1.13; Z = 0.55; P = .58).
LIMITATIONS:
Only case-control studies, which may be subject to bias, met the inclusion criteria for this meta-analysis.
CONCLUSIONS:
Vertex pattern AGA was associated with a significant increased risk of prostate cancer. Any pattern AGA did not show a significant increase in the risk of prostate cancer.

Does this explain why propecia is said to mostly only work on the vertex and not the temples?

Seems like the pattern of the AGA might help determine what's causing it?

Interesting results.

CS, I've been meaning to ask you this for long- what is the difference in mechanisms of vertex and the frontal (the recession mpb) baldness? Are different factors at play? Is Insulin resistance a factor in the first and not in the second? Any other light you can throw on these two types of hairloss would be welcome.

For the record, I'm in the frontal recession category.

9rugrats5 - In an attempt to answer this question, I will first show a study that contradicts the vertex factor. The details within this study are important for hair splitting. Bear in mind that many similar studies are grouping these men together looking for links, however it's probably a little more complicated.

There are two other studies which show tendencies in other areas. In my opinion, frontal balding, if one just examines the most prevalent factors involves stress hormones and neuropeptides. 5-AR block-aid would help with frontal, however there is also the two former factors to consider also.

Int J Cancer. 2007 Feb 15;120(4):776-80.
5alpha-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia.
Hayes VM, Severi G, Padilla EJ, Morris HA, Tilley WD, Southey MC, English DR, Sutherland RL, Hopper JL, Boyle P, Giles GG.

Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia. v.hayes@garvan.org.au

Controversy exists over the significance of associations between the SRD5A2 (5alpha-reductase type 2) polymorphisms, A49T and V89L, and risk of prostate cancer. These potentially functional polymorphisms may alter life-long exposure to androgens with subsequent effects on male health and aging. The aim of this study was to examine the association of these variants with prostate cancer risk, plasma hormone levels and androgenetic alopecia. Subjects include 827 cases and 736 controls from an Australian population-based case-control study of prostate cancer. Information on prostate cancer risk factors and patterns of balding were collected. Plasma levels of testosterone, 3alpha-diol glucuronide (3alpha-diolG), dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin and estradiol were measured for controls. No associations with the V89L polymorphism were found. Carriers of the rarer A49T A allele were at a 60% higher risk of prostate cancer (OR = 1.60; 95% CI 1.09-2.36; p = 0.02) and 50% lower risk of vertex and frontal balding (p = 0.03) compared with men homozygous for the more common G allele. Although we found little evidence of association between this variant and plasma levels of 5 measured androgens, circulating 3alpha-diolG levels were 34% lower in A49T A allele carriers (p < 0.0001). Our study provides evidence that the SRD5A2 A49T A variant is associated with an increased risk of prostate cancer, lower levels of circulating 3alpha-diolG and decreased risk of baldness. These findings raise important questions with respect to previous assumptions concerning hormonal influences on prostate cancer risk in ageing males.

Now a study that links increased risk of frontal balding:

J Clin Endocrinol Metab. 2006 Nov;91(11):4205-14.
Extensive clinical experience: nonclassical 21-hydroxylase deficiency.
New MI.

Adrenal Steroid Disorders Program, Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA. maria.new@mssm.edu
Erratum in
J Clin Endocrinol Metab. 2007 Jan;92(1):142. Dosage error in article text.

CONTEXT:
Nonclassical congenital adrenal hyperplasia (CAH) owing to steroid 21-hydroxylase deficiency (NC21OHD) is the most frequent of all autosomal recessive genetic diseases, occurring in one in 100 persons in the heterogeneous New York City population. NC21OHD occurs with increased frequency in certain ethnic groups, such as Ashkenazi Jews, in whom one in 27 express the disease. NC21OHD is underdiagnosed in both male and female patients with hyperandrogenic symptoms because hormonal abnormalities in NC21OHD are only mild to moderate, not severe as in the classical form of CAH. Unlike classical CAH, NC21OHD is not associated with ambiguous genitalia of the newborn female.
MAIN OUTCOME MEASURES:
The hyperandrogenic symptoms include advanced bone age, early pubic hair, precocious puberty, tall stature, and early arrest of growth in children; infertility, cystic acne, and short stature in both adult males and females; hirsutism, frontal balding, polycystic ovaries, and irregular menstrual periods in females; and testicular adrenal rest tissue in males.
CONCLUSIONS:
The signs and symptoms of hyperandrogenism are reversed with dexamethasone treatment.

Full study: http://jcem.endojournals.org/content/91/11/4205.long

Some background on this 1 out of 100 people disorder, known as Classical and Nonclassical 21-Hydroxylase Deficiency

CAH refers to a family of inherited disorders in which defects occur in one of five enzymatic steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, ACTH levels rise via a negative feedback system and stimulate adrenal hormone secretion, resulting in hyperplasia of the adrenal cortex. In 21OHD, responsible for 90–95% of CAH cases, there is an accumulation of the precursors immediately proximal to the 21-hydroxylation step in the pathway of cortisol synthesis, and these precursors are shunted into the androgen pathway

http://jcem.endojournals.org/content/91/11/4205/F1.expansion.html

Br J Dermatol. 2003 Dec;149(6):1207-13.
Androgenetic alopecia in men aged 40-69 years: prevalence and risk factors.
Severi G, Sinclair R, Hopper JL, English DR, McCredie MR, Boyle P, Giles GG.

Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.

BACKGROUND:
The epidemiology of androgenetic alopecia (AGA) is not fully understood. Although a strong genetic basis has long been identified, little is known of its non-genetic causes.
OBJECTIVES:
To estimate the prevalence of and to determine risk factors for AGA in men aged 40-69 years in Australia.
METHODS:
Men (n = 1390) were recruited at random from the electoral rolls to serve as controls in a population-based case-control study of prostate cancer. All were interviewed in person and direct observations of AGA were made. Men were grouped into the following categories; no AGA, frontal AGA, vertex AGA and full AGA (frontal and vertex AGA). Epidemiological data collected from these men were used for an analysis of risk factors for each AGA category using unconditional logistic regression with AGA category as the response variable adjusting for age, education and country of birth.
RESULTS:
The prevalence of vertex and full AGA increased with age from 31% (age 40-55 years) to 53% (age 65-69 years). Conversely, the proportion of men with only frontal AGA was very similar across all age groups (31-33%). No associations were found between pubertal growth spurt or acne, reports of adult body size at time of interview, urinary symptom score, marital status, or current smoking status or duration of smoking and the risk of any form of AGA. The consumption of alcohol was associated with a significant increase in risk of frontal and vertex AGA but not full AGA. Men with vertex AGA had fewer female sexual partners but average ejaculatory frequency did not differ between men in different AGA categories. Reported weight and lean body mass at reaching maturity at about 21 years of age were negatively associated with vertex balding (P for trend < 0.05) but not with frontal AGA or full AGA.
CONCLUSIONS:
Evidence for environmental influences on AGA remains very slight. Our study failed to confirm previously reported or hypothesized associations with smoking and benign prostatic hypertrophy. The associations that we found with alcohol consumption and with lean body mass at age 21 years would be worthy of further research if they were able to be replicated in other studies.

Thanks CS. On the back of this info, are there supplements from your regimen that you would emphasize as being the most important for frontal vs diffuse/vertex? I know that methylation was also a factor, correct? Thank you in advance

CausticSymmetry wrote:In my opinion, frontal balding, if one just examines the most prevalent factors involves stress hormones and neuropeptides. 5-AR block-aid would help with frontal, however there is also the two former factors to consider also.

Thanks, CS, that took some time to read and understand. I found the post quite informative. Particularly the image you linked helps in understanding better. Here it is again for those who missed it. http://jcem.endojournals.org/content/91/11/4205/F1.large.jpg

So, in frontal recession type of AGA, there is a good chance that the 21-hydroxylase step could be misfiring, meaning the presence of cortisol precursors in the body may be greater than normal due to faulty conversion to cortisol. So, bad adrenals (or fatigue) could be a big factor in frontal recession, as it may be indicative of hyperplasia of the adrenals.

To pick your mind further, are the 5-AR enzyme blockers same as the DHT blockers? What pathways are taken when this T to DHT conversion is inhibited, what happens to the precursors then?

And instead of blocking 5-AR, could its production be attenuated? As a layman's resource, I resort to wikipedia on 5-AR, "The enzyme is produced in many tissues in both males and females, especially in the reproductive tract, testes and ovaries, skin, seminal vesicles, prostate, epididymis and many organs." Could this, then, give credence to the theory that abstinence might help in reducing (frontal) mpb. Could reduced sexual activity mean lower generation of 5-AR? If 5-AR production and sexual activity show correlation, could it even mean that higher than average secretions of 5-AR may lead to overactivation of T/DHT pathway and underconversion to cortisol?

As an aside, this means that the TCM theory of linking AGA to kidney Qi has much merit.

What would be natural treatment for genetic defects as NC21OHD in CAH?

There are studies that actually show dexamethasone - glucocorticoid to be effective for treating women and the same seem to apply also for - polycystic ovarian syndrome PCOS (that i'd assume is a logical expression of the condition over time).

For the last, the linkage is also with C677T MTHFR gene in some population groups with the CAH/PCOS conditions, including hirtuism. For the lastest, hirtuism being related with excess teststerone in woman, and interstingly by that even increased sexual drive, well being and feel good make the story all the different for the man.

http://www.ncbi.nlm.nih.gov/pubmed/22870016


I am wondering what link would adressing MTHFR mutations provide on stabilisation and rebuilding of the adrenal cortex hormones and by this addresing also the NC210HD - CAH conditions. Any ideas? My pros are that metal toxicity is often found in those with CAH or PCOS and the relieving toxic burden, and improve immunity) is pro health thing one is getting from it. This is where also advocating iodine by dr. Flatcher takes place on including blood sugar regulation the very next mechanism supp is suppose to help with.

http://pcoslady.wordpress.com/tag/iodine-pcos/

https://sites.google.com/site/miscarriageresearch/supplements-and-miscarriage/d-chiro-inositol

Myo-Inositol has also some studies that show it to be as effective treatment, but with a whole different mechanism. Comparing apples and oranges or there is common way to address man and woman problems due the same genetic mutations with the same steps?

I found this interesting:
Myo-inositol is inverse marker for diagnosing prostate cancer. Note that Myo-inositol is a bit different to IP6 often discused form of inositol.

http://www.ncbi.nlm.nih.gov/pubmed/18213632

Myo-inositol on insulin and diabetes

http://www.ncbi.nlm.nih.gov/pubmed/838172

Effects of myoinositol on sperm mitochondrial function in-vitro.

http://www.ncbi.nlm.nih.gov/pubmed/21434479

And as libido booster due diabetes
http://www.ncbi.nlm.nih.gov/pubmed/17121317

What about hair growth and myo-inositol?
I'd say it's a cheap supplement worth trying: http://www.iherb.com/Jarrow-Formulas-Inositol-750-mg-100-Veggie-Caps/192

bump

Really, nobody here is interested in myoinositol for the overall anti ageing effect, directly connected with a man's health?

I've looked at this in depth some years ago on the forum. Everything on this thread is worth a good look, because as mentioned, the forum waxes and wanes on various topics. This one really hits hard on why managing stress and its hormones really makes a difference.

PCOS for women, or for men with excessive cortisol and androgens want to tame cortisol.

Front Biosci. 2006 Sep 1;11:2230-48.
Corticotropin releasing hormone and the skin.
Slominski A, Zbytek B, Zmijewski M, Slominski RM, Kauser S, Wortsman J, Tobin DJ.

Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. aslominski@utmem.edu

Cotricotropin-releasing hormone (CRH) and related peptides are produced in skin that is dependent on species and anatomical location. Local peptide production is regulated by ultraviolet radiation (UVR), glucocorticoids and phase of the hair cycle. The skin also expresses the corresponding receptors (CRH-R1 and CRH-R2), with CRH-R1 being the major receptor in humans. CRH-R1 is expressed in epidermal and dermal compartments, and CRH-R2 predominantly in dermal structures. The gene coding for CRH-R1 generates multiple isoforms through a process modulated by UVR, cyclic adenosine monophosphate (cAMP) and phorbol 12-myristate 13-acetate. The phenotypic effects of CRH in human skin cells are largely mediated by CRH-R1alpha through increases in concentrations of cAMP, inositol triphosphate (IP3), or Ca2+ with subsequent activation of protein kinases A (PKA) and C (PKC) dependent pathways. CRH also modulates the activity of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappaB), activator protein 1 (AP-1) and cAMP responsive element binding protein (CREB). The cellular functions affected by CRH depend on cell type and nutritional status and include modulation of differentiation program(s), proliferation, viability and immune activity. The accumulated evidence indicates that cutaneous CRH is also a component of a local structure organized similarly to the hypothalamo-pituitary-adrenal axis.

Full study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847336/

Nice insight, tnx for sharing CS.

Interesting there is UV light with special importance. Never thought about it before.  Another thing also what comes to mind is UV-b radiation one gets from Violet Ray when sparking the scalp probably goes about the same mechanism. However, we should know more precise about the spectrum to be making some serious statements about it. But yes, sparking is source of UVR, regardless of the type of electrode used...

In human skin CRH production is regulated by environmental and other factors, i.e., ultraviolet radiation and forskolin stimulate CRH production, while dexamethasone inhibits it (66, 67). Most recently we have produced new data documenting UVB stimulation of CRH production in epidermal melanocytes (Zbytek et al, in preparation). Thus, UVB stimulated gene transcription, with translation of the corresponding message, and secretion of CRH peptide into the extracellular environment. This effect was time and dose dependent (Zbytek et al, in preparation). In cultured dermal fibroblasts, UVB similarly stimulated CRH production and release, and increased POMC expres​sion(Figure 10).

Other than that, do you have any experiences and anecdotes with different types of inositol, (IP3, IP6, myo-inositol, D-chiro inositol)? There might be many more mechanisms of why different types of inositol would work differently in man or women. From what i've gathered, for some this could be very worth looking product(s) for over all anti-aging benefits that relate to hair growth as well. For example Lithium is used for treating Alzheimers, by the mechanism of decreasing IP3 turnover and thus regulating calcium levels. IP6 is known for its anticancer and chelating benefits, myo and chiro relate to the prostate health and in women PCOS reversal, along with overall insulin regulating benefits (i am specially interested in). I am this |<--->| close to buy a few bottles for myself and my girl, but want to see some more data first. I've used IP6 before, for iron lowering purpose and kind of liked it...

Beebrox - The short story on inositol in my experience is, the cheap stuff works. In fact, there's really no need to buy the more expensive D-chiro inositol, so just any plain inositol will work. Definitely worth a short. It doesn't work for everyone of course, but when it does, it's worth a try.

I think chronic muscle tension may play a role in prostate cancer as well; high tone pelvic floor dysfunction is the presence of chronically tight pelvic floor muscles, which can choke off the blood supply to the prostate. I bet there is a general correlation to scalp tightness and pelvic floor tightness; I know there is for me.

SlowMoe - That is an interesting observation. I think a rebounder really helps with vein strengthening, and probably provides a boost to pelvic health.

And stability exercises for the lower abdominal area like plank and various yoga acts...

I'd like to know some more specific information on the DNA binding proteins in this area of the scalp. One of the postulates for the pattern of MPB has to do with the tri-nucleotide repeats on the androgen receptor gene, and the hypothesis is that for the CAG repeat sequence (coding for other proteins that interact with the androgen receptor besides androgen itself), that the DNA binding proteins in the scalp are different so the picture of proteins interacting with the androgen receptor in the scalp is different than the rest of the body. If this were true, it might help explain why we lose hair in this area of the scalp and would also connect this to increased androgen sensitivity that may also translate to the prostate. The whole of the microenvironmental interactions would have to be looked at too though, because why are DNA binding proteins different here in the scalp (oxidative stress vulnerability? blood flow?), and why does this translate to hypertrophy in the prostate and atrophy in the hair?

Wish I had a lot of money and a proper facility to do that kind of testing,   . Either way, interesting study CS. Thanks sir. Not sure how I missed this one.

CausticSymmetry wrote:SlowMoe - That is an interesting observation. I think a rebounder really helps with vein strengthening, and probably provides a boost to pelvic health.

Do you think a full sized trampoline has the same effect?

SlowMoe wrote:I think chronic muscle tension may play a role in prostate cancer as well; high tone pelvic floor dysfunction is the presence of chronically tight pelvic floor muscles, which can choke off the blood supply to the prostate. I bet there is a general correlation to scalp tightness and pelvic floor tightness; I know there is for me.

Same in my case....

Complexx wrote:

SlowMoe wrote:I think chronic muscle tension may play a role in prostate cancer as well; high tone pelvic floor dysfunction is the presence of chronically tight pelvic floor muscles, which can choke off the blood supply to the prostate. I bet there is a general correlation to scalp tightness and pelvic floor tightness; I know there is for me.

Same in my case....

Dude, check your PM's