Male Pattern Baldness

What is male pattern baldness?

Male pattern baldness is caused by a genetic sensitivity of hair follicles to DHT. This hormone causes follicles to shrink or "miniaturize". In turn, this shortens their lifespan and prevents them from producing hair normally.

5-alpha-reductase

5-alpha-reductase (5-AR) is an NADPH-dependent enzyme which converts testosterone to DHT. Three isoenzymes of 5 alpha-reductase enzyme are recognised

• type 1 - which is located on the short arm of chromosome 7 and occurs in non genital skin, scalp, in the sebaceous gland, in the liver and in the brain
• type 2 - which is located on the short arm of chromosome 2 and occurs mainly in the prostate, genital skin, seminal vesicles and in the dermal papilla Occhiato et al.
  • testosterone has a much higher affinity for this type 2 than for type 1
• type3 is also required for the glycosylation, it converts polyprenol to dolichol

Men with androgenic alopecia typically have higher levels of 5-alpha-reductase, lower levels of total testosterone, higher levels of unbound/free testosterone, and higher levels of total free androgens including DHT.

• On the same scalp, balding skin has more 5-AR activity than non-balding skin. Puerto and Mallol

In 5 alpha-reductase deficiency (5-ARD), the type 2 isoenzyme is that which is lacking. Men with this condition do not develop male-pattern baldness despite evidence that the type 1 isoenzyme is the dominant form in the adult male scalp, and in 5 alpha-reductase deficiency, this isoenzyme is present at normal levels. Thus, one must conclude that the type 2 5-AR is necessary to the development of male pattern baldness ref. This conclusion doesn't sound justified, and dutasteride which inhibits type 1 too is more effective than finasteride which inhibits type 2.

The only recognized, effective way for slowing down male pattern baldness is by inhibiting 5-AR type 2 via Finasteride or similar drug. Therefore, it is important to have an overview on what inhibits or promotes 5-AR.

Inhibition

• Synthetic drug Finasteride inhibits type 2 and 3
  • 5 mg per day is able to reduce about 70% of the serum DHT concentration Occhiato et al.
• Synthetic drug Dutasteride inhibits all types of 5-AR
  • Dutasteride is considered more effective at 0.1mg than Finasteride at 5mg doses, so it is possible that actually inhibiting type 1 is more important than type 2
  • 90% reduction of serum DHT (dosage not mentioned)
• Alfatradiol/Pantostin is topical ethanolic solution that inhibits 5-AR when applied on the scalp. The ethanol can irritate the skin.
  • Minoxidil is more effective, but at least Alfatradiol decreases hair loss Blume-Peytavi et al.
  • No prescription is needed in Germany, so it's fairly safe, besides the possibility of skin irritation.

• Zinc sulphate and azelaic acid inhibit 5-AR in human skin in vitro. Adding B6 increases the effect of zinc. A combination of the three in low amounts achieved 90% inhibition of 5-AR. Stamatiadis et al
• Saw palmetto and beta-sitosterol Prager et al.
• Unsaturated fatty acids gamma-linolenic, alpha-linolenic, linoleic, and oleic acid Liang and Liao
• Medium chain fatty acids found in coconut oil, palm kernel oil, as well as unsaturated alpha-linolenic and oleic Liu et al.
• Various polyphenols Hiipakka et al.
  • Green tea catechin (-)-epigallocatechin gallate (EGCG) shows potent inhibition in cell-free but not in whole-cell assays of 5-AR
  • type 1 inhibitors: myricetin, quercitin, baicalein, and fisetin; alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates
  • type 2 inhibitors: biochanin A, daidzein, genistein, and kaempferol
• Cream containing honokiol Bernard et al.
  • Collection of research on honokiol, not necessarily related to hair loss
• Ganoderic acid (in Reishi mushroom) Liu et al.

Promotion

• 6-month dietary vitamin E (VE) deficiency in rats resulted in a twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene Fischer et al.
• Hyperinsulinemia
  • elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells. Kayampilly et al., Another paper
  • acutely enhances ACTH effects on both the androgen and glucocorticoid pathways that suggest insulin stimulation of 5 α-reductase activity Tosi et al.
• A diet only deficient in linoleate causes mild skin scaling and hair loss in mice Cunnane and Anderson (note: not clear if it's due to 5-AR promotion, move to some other section)

3beta-HSD

The 3beta-HSD isoenzymes catalyze an obligatory step in the biosynthesis of androgens, estrogens, mineralocorticoids and glucocorticoids.

• There is substantially increased activity of 3beta-HSD in balding than in non-balding scalps Sawaya et al.
  • The increased conversion of DHEA to 3H-delta 4-androstenedione may be a critical step for androgenic action and may be responsible for excessive androgenicity in male-pattern baldness.

PGD2

Recent research suggests that elevated levels of the enzyme prostaglandin D2 synthase and its product prostaglandin D2 (PGD2) in hair follicles causes androgenetic alopecia. Garza A et al

• Prostaglandin D2 synthase (Prostaglandin-H2 D-isomerase (PTGDS) = H-PGDS) converts prostaglandin H2 (PGH2) into prostaglandin D2 (PGD2), so maybe a topical inhibitor of this enzyme will do the trick (to compensate for the elevated level of this enzyme).
  • HQL-79 is a well known, but relatively weak H-PGDS inhibitor. Aritake K et al
  • Scientists seem to have designed much more potent H-PGDS inhibitors. Kamauchi S et al
  • More H-PGDS inhibitors here, but no formulae are provided "The formulae of the inhibitors are proprietary information"Takahashi S et al
  • TFC-007 is a selective H-PGDS inhibitor. Nabe T et al

• H-PGDS levels also seem to decrease rapidly (through the ubiquitin-proteasome system) when intracellular calcium is increased Yazaki M et al Free full text
  • but (the required) calcium ionophores (to increase intracellular calcium locally) also seem to promote tumors. Kumar S et al

DHEA(S)

The skin is capable of synthesizing active androgens, such as DHT, from the systemic precursor DHEA-S. The first step in this pathway is the desulfatation of DHEA-S by the enzyme steroid sulfatase (STS). STS deficiency manifests with dry, scaly skin.

• Elevation of DHEA-S is associated with male pattern baldness in young men The biochemistry of androgens, particularly dehydroepiandrosterone sulfate, suggests that adrenal hyperactivity may initiate alopecia in young men who are genetically susceptible. Pitts
• Acute and chronic stress increase DHEAS concentrations in rhesus monkeys Maninger et al.
  • Like cortisol, DHEAS concentrations showed a diurnal rhythm with higher concentrations in the morning compared to the evening and a decrease in response to dexamethasone (DEX) administration.
• Regular exercise and calorie restriction increase DHEA.

Diet

The wai diet for now seems like a very good diet for managing male pattern baldness.

• High-frequency, low glycemic meals of OJ + olive oil would avoid insulin spikes (shown to stimulate 5-AR)
• Oleic/linoleic acids, as well as polyphenols in olive oil would inhibit 5-AR to an extent.
• Antioxidants in fruits would help to cope with inflammation, which is present in the scalp of those with androgenic alopecia as shown by the higher levels of PGD2.
• Vitamin E (or any other vitamin) deficiency is unlikely.
• Beta-sitosterol is found in avocados and cashews (wai foods), and pumpkin seeds (non-wai that might be somewhat acceptable)