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, as well as androstenedione to 5alpha-androstanedione. 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.

17beta-HSD

High enzyme activity may be related to higher degrees of balding (Hodgins et al.)

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

• Topical Cetirizine may be an appropriate solution to fight PGD2 in the scalp. idea
  • Histamine release was not altered by cetirizine treatment, but prostaglandin D2 (PGD2) production, which peaked at 3 to 5 hours, was clearly reduced by cetirizine treatment, being lower at all time points during the reaction Charlesworth et al.
  • Recipe to make at home: 50 tabs cetirizine, 50 ml of distilled water, 30 ml of ethanol (70%), Propylene glycol 20 ml

COX

1. COX converts arachidonic acid (AA, an omega-6 PUFA) to prostaglandin H2 (PGH2), the precursor of the series-2 prostanoids.
   1. COX-2 expression in skin is induced by UVB exposure Buckman et al.
2. Lipocalin-type PGD2 synthase (L-PGDS) or hematopoietic (H)-PGDS converts PGH2 to PGD2
3. PGD2 undergoes sequential non-enzymatic dehydration reactions to form 15d-PGJ2 Scher and Pillinger
4. 15d-PGJ2 is deomonstrated to suppress hair growth and is implicated in male pattern baldness.
   1. Toxicity of 15d-PGJ2 to mOP cells is related to intracellular Glutathione levels Zhongmin et al.

• Topical Ibuprofen could be another alternative for fixing inflammation, Ibuprofen is COX inhibitor.
  • Topical Ibuprofen penetrates 0.5cm in the skin

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. Excess DHEA is related to oily skin, immune hyperactivity and insulin resistance.

• 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)