Recently, I was extremely fortunate to have a dump truck of papers I've been itching to read delivered to my inbox. The most notable was Paul Taylor's 2009 paper, Big head? Bald head? Skull expansion: alternative model for the primary mechanism of androgenic alopecia.
In the paper, Taylor progresses a heretical view of pattern baldness that moves the genetic-androgen hypothesis out of the dark ages. While I think the theory is imperfect, it does fill in many gaps in my own understanding of scalp anatomy, strengthening the bioenergetic view of pattern hair loss I formally began writing about in 2013, with the publication of HAIR LIKE A FOX: A Bioenergetic View of Pattern Hair Loss.
Let's take a second and run through some highlights from the paper.
AGAINST THE MAINSTREAM
Taylor appears to be among the few hair loss researchers who does not unconditionally support the genetic-androgen hypothesis.
Laying waste to the so-called "androgen paradox," Taylor states the obvious:
In addition, he identifies a monumental obstacle for those who subscribe to the genetic-androgen hypothesis, i.e., the unknown mechanism of how the androgen, dihydrotestosterone (or DHT) terminates hair follicles:
BALDNESS AS A RESULT OF SKULL EXPANSION?
Much like the bioenergetic theory of pattern hair loss, the skull expansion theory attempts to explain nuances of baldness that are minimized or ignored in the traditional genetic-androgen hypothesis.
The skull expansion theory suggests that baldness is the result of an exaggeration of the bone remodeling process causing a reduction in blood supply to the capillary network within the balding area of the scalp.
Instead of an accumulation of DHT within the hair follicle — which doesn't explain the typical "horseshoe" pattern of baldness — DHT increases the growth of the frontal and parietal regions of the scalp, cutting off the blood supply to the hair follicles.
The temporal (sides of the head) and occipital (back of the head) regions of the scalp are protected from hair loss because they are closer to the main arterial blood supply. However, the frontal and parietal regions are more remote — and therefore more susceptible to baldness.
PROBLEMS WITH THE SKULL EXPANSION THEORY
Perhaps unavoidably, the author subscribes to the idea that women are protected from hair loss due to their higher levels of estrogen, the so-called "female hormone."
The skull expansion theory of pattern hair loss proposes that DHT supports hair growth, however, because it's anabolic and increases bone growth — which is believed to be "exaggerated" in pattern hair loss — it leads to hair loss indirectly by expanding the skull and smothering blood capillaries.
Similarly, because estrogen dissolves bone, it would appear that estrogen is not only a candidate for the reason why women are more protected from pattern baldness than men, but possibly as a therapy.
This is probably were the skull expansion theory veers off course and is no longer useful.
For instance, in 2007 it was found that balding men had a 5% lower bone mineral density than non-balding men, perhaps suggesting that whatever is bad for bone is also bad for hair growth.
Although, topical estrogen does appear to increase the rate of hair growth is some situations, possibly due to an increase in mitosis, a "higher functioning" of estrogen is implicated in the genesis of pattern baldness in a few ways.
ESTROGEN AND BALDNESS
Consider estrogen's effects on the capillary network, which was fond to be almost completely destroyed in late stage pattern baldness. Estrogen causes systemic capillary leakiness, which is corrected by progesterone, a hormone that opposes estrogen.
The reduction in scalp blood flow, and scalp hypoxia in baldness may also be attributed to estrogen's effects on the metabolism. For example, by interfering with oxidative metabolism, and the subsequent production of carbon dioxide, estrogen tends to reduce peripheral blood flow and induce hypoxia in tissues.
The overproduction of collagen seen in the scalps of those with pattern baldness might also be attributed to estrogen. By stimulating a cell beyond its ability to meet energy demands, estrogen tends to cause cells overproduce collagen, and uptake calcium — "...the final common path to cell aging and death." If a larger skull is a feature of pattern baldness, perhaps the accumulation of collagen and calcium could offer an explanation.
In 2012, Garza, et al's discovery that prostaglandin d2 accumulated in the scalp's of balding men and inhibited hair growth created a tidal wave of interest in inhibiting its synthesis. However, it appears that few people read further than the headline, as basic investigation reveals the role of estrogen in activating the phospholipase enzymes, which degrade the so-called "essential fat," arachidonic acid, into the pro-inflammatory prostaglandins.
Additionally, a few hormones associated with baldness (e.g., aldosterone, cortisol, and prolactin) are all increased by estrogen.[11,12,13,14,15,16]
MORE SUPPORT FOR A BIOENERGETIC VIEW OF PATTERN HAIR LOSS
The bioenergetic view of baldness proposes that environmental-driven interferences in energy metabolism (i.e., glucose to lactic acid), leads to unfavorable changes in the scalp (e.g., edema, oxidative stress, fibrosis), which inhibits hair growth overtime.
The complex biochemical web of stress, hormones, and signaling substances in pattern baldness can be viewed simply within the context of how cells make energy, which is largely regulated by thyroid hormones.
In 2013, Vidali, et al found that hair aging was caused by a decline in mitochondrial function. They referred to thyroid hormones as, "mitochondrial hair medicine."
The remoteness of the capillary network within balding regions of the scalp, as pointed out by Taylor, and the tendency of stress to limit peripheral tissues response to thyroid hormone, would provide an explanation of how the delicate mini-organ — which is inherently inefficient converting proportionately more glucose to lactic acid than carbon dioxide — loses coherence overtime.
If energy metabolism has been chronically interfered with, for instance by the accumulation of polyunsaturated fats in the tissues (and their end products, e.g., the prostaglandins, acrolein, malondialdehyde, hydroxynonenal, crotonaldehyde, ethane, pentane, and the neuroprostanes), we can expect that the energy-hungry hair follicle will degrade in function, taking on characteristics of other tissues deprived of energy such as edema, oxidative stress, and fibrosis.
If this theory of hair loss proves to be accurate, easy-to-digest nutrition that supports the rate of metabolism (e.g., salt, fructose, gelatin, milk, cheese, beef liver, oysters, etc.) and simple supplements such as thyroid hormone, caffeine, aspirin and vitamin K would seem useful in the fight against pattern hair loss by restoring "efficient" (i.e., glucose to carbon dioxide) energy generation.
- Martina, W., et al. Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci U S A. Jun 5, 2001; 98(12): 6871–6876. "Estrogen treatment accelerated the senescent decline [of bone] in all of these parameters."
- Crovato, F., et al. Histochemistry of Dermis and Blood Vessels in Male Pattern Alopecia. Biopathol- ogy of Pattern alopecia, pp. 191-199. Karger, Basel/New York 1968.
- Ziylan, Y.Z., et al. Blood-brain barrier permeability: regional alterations after acute and chronic administration of ethinyl estradiol. Neurosci Lett. 1990 Oct 16;118(2):181-4. "Three weeks treatment but not the single injection of ethinyl estradiol produced significant increases in the cerebrovascular permeability-surface area product for sucrose and inulin in almost all brain regions."
- Lagrue, G., et al. [Ovarian function in orthostatic idiopathic edema. Oral administration of progesterone and changes in capillary permeability]. Presse Med. 1983 Dec 10;12(45):2859-62. "In virtually all patients the initial disorder in capillary permeability, as evaluated by Landis' isotopic test, was fully corrected by progesterone administered orally."
- Klemp, P., et al. Subcutaneous blood flow in early male pattern baldness. J Invest Dermatol. 1989 May;92(5):725-6. "This difference was statistically significant (p much less than 0.001). A reduced nutritive blood flow to the hair follicles might be a significant event in the pathogenesis of early male pattern baldness."
- Goldman, B.E., et al. Transcutaneous PO2 of the scalp in male pattern baldness: a new piece to the puzzle. Plast Reconstr Surg. 1996 May;97(6):1109-16; discussion 1117.
- Gross. Reproductive cycle biochemistry. Fertility & Sterility 12(3), 245-260, 1961. "The maintenance of an environment conducive to anaerobic metabolism--which may involve the maintenance of an adequate supply of the substances that permit anaerobiosis...seems to depend primarily upon the action of estrogen.” "Glycolytic metabolism gradually increases throughout the proliferative phases of the cycle, reaching a maximum coincident with the ovulation phase, when estrogen is at a peak. Following this, glycolysis decreases, the respiratory mechanisms being more active during the secretory phase. Eschbach and Negelein showed the metabolism of the infantile mouse uterus to be less anaerobic than that of the adult. If estrogen is administered, however, there is a 98 per cent increase in glycolytic mechanisms.” "The effect of the progestational steroids may be such as to interfere with the biochemical pattern required for support of this anaerobic environment.”
- T. Fujita, "Calcium, parathyroids and aging," in Calcium-Regulating Hormones. 1. Role in Disease and Aging, H. Morii, editor, Contrib. Nephrol. Basel, Karger, 1991, vol. 90, pp. 206-211. "All cell death is characterized by an increase of intracellular calcium...." "Increase of cytoplasmic free calcium may therefore be called 'the final common path' of cell disease and cell death. Aging as a background of diseases is also characterized by an increase of intracellular calcium. Diseases typically associated with aging include hypertension, arteriosclerosis, diabetes mellitus and dementia."
- Garza, L.A., et al. Prostaglandin d2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012 Mar 21;4(126):126ra34.
- Periwal, S.B., et al. Effect of hormones and antihormones on phospholipase A2 activity in human endometrial stromal cells. Prostaglandins. 1996 Mar;51(3):191-201. "Estradiol produced a significant stimulatory effect (P < 0.001) on phospholipase A2 activity in predecidual cells, and this effect was antagonized by tamoxifen."
- Arias-Santiago, S., et al. Br J Dermatol. 2009 Nov;161(5):1196-8. Epub 2009 Jun 9. Elevated aldosterone levels in patients with androgenetic alopecia. "Patients with AGA showed significantly higher systolic blood pressure values (136.23 vs. 124.10 mmHg, P = 0.01) and aldosterone levels (197.35 vs. 133.71 pg mL(-1), P = 0.007) vs. controls."
- Schmidt JB. Hormonal basis of male and female androgenic alopecia: clinical relevance. Skin Pharmacol. 1994;7(1-2):61-6. "Our findings showed a significant elevation of F [CORTISOL] in both male and female AH patients compared to controls, pointing to the suprarenes as a contributing factor in AH. This is confirmed by the observation of exacerbated AH in periods of increased stress."
- Stárka, L., et al. Hormonal profile of men with premature balding. Exp Clin Endocrinol Diabetes. 2004 Jan;112(1):24-8. "A borderline significant trend was recorded with respect to increased levels in 17OH-P and prolactin."
- Bekker and Svechnikova. [Sex and age differences in the peripheral blood aldosterone levels]. Probl Endokrinol (Mosk). 1981 Sep-Oct;27(5):42-5. "An increase in the blood aldosterone content in menopause appears to be due to the hyperestrogenic phase (the first menopausal phase in women) and estrogen-stimulated aldosterone synthesis. Sexual differences in aldosterone secretion disappear with age. Aldosterone content is significantly lower in males and females, age over 80 years, than that in younger subjects, and sexual differences are absent."
- Caticha O, Odell WD, Wilson DE, Dowdell LA, Noth RH, Swislocki AL, Lamothe JJ, Barrow R. Estradiol stimulates cortisol production by adrenal cells in estrogen-dependent primary adrenocortical nodular dysplasia. J Clin Endocrinol Metab. 1993 Aug;77(2):494-7. "Adrenal glands from a patient with ACTH-independent Cushing's syndrome, whose symptoms worsened during pregnancy and oral contraceptive use, were cultured in different concentrations of estradiol. Estradiol stimulated cortisol secretion in a dose-response manner in the absence of ACTH. Since immunoglobulins G from this patient did not stimulate corticosterone production in a mouse adrenal bioassay, an adrenal-stimulating immunoglobulin is unlikely to be the cause of adrenal hyperfunction in this case. This is the first description of estradiol stimulation of cortisol production by cultured adrenal cells in ACTH-independent Cushing's syndrome."
- Nicoletti, I., et al. Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation. Acta Endocrinol (Copenh). 1984 Feb;105(2):167-72. "A case of a patient with hypopituitarism due to a disturbance of hypothalamo-pituitary regulation is presented, who developed high-grade hyperprolactinaemia after the initiation of substitutive therapy with testosterone esthers. The increase in serum Prl was strictly related to testosterone aromatization to oestradiol, since anti-oestrogen compounds were effective in reducing (clomiphene) or abolishing (tamoxifen) the enhanced Prl secretion. The oestrogen effect in raising Prl release was not attributable to a reduction in the dopamine inhibition of Prl-secreting cells, as the dopamine-antagonist domperidone failed to increase Prl serum levels in the same patient. This suggests that, in man, the oestrogen effect in enhancing Prl release is mainly enacted directly on the pituitary lactotrophs rather than exerted through a reduction in the hypothalamic dopamine activity."
- Denckla WD. Pituitary inhibitor of thyroxine. Fed Proc. 1975 Jan;34(1):96. "A description is given of a new pituitary function. It is suggested that the new function acts to decrease gradually the responsiveness of the peripheral tissues to thyroid hormones throughout life. It is suggested that the postulated relative hypothyroidism of older animals might contribute to their loss of viability."