- In 1942 Dr. James B. Hamilton changed the course of hair loss research with his groundbreaking study in a group of 104 men who failed to mature sexually (i.e., eunuchs or eunachoids).1 Both young and old, the men were unified by testicular insufficiency, which Dr. Hamilton found to give rise to three anomalies: 1. A lack of balding and retention of all scalp hair. 2. Less sebaceous gland activity, compared to normal men of comparable age, that resulted in a reduced oiliness of the face, hair, and scalp and a complete lack of acne. 3. Dandruff that was either absent or present in such small amounts such that only a few white flakes could be brushed off from the scalp. In stark contrast, mature young men of the same age had copious amounts of dandruff.
- Independent research on the side effects of Finasteride found that in a small study of 72 participants, 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm.8
- balding is increasingly becoming a metabolic marker for future and current health problems, including metabolic syndrome,12 insulin resistance,13,14 hyper20 tension,15,16 polycystic ovarian syndrome,17,18 heart disease,19 and cancer.
- Other clinical studies had confirmed that young children’s fingers cleanly sheared off beyond the outermost crease of the outermost joint would invariably regrow perfectly in about three months.3 When a probe was moved across the surface of the wounds of 10 children 26 who had finger tip amputations, the currents recorded were remarkably similar to those obtained by Borgens et al. (1977) on salamanders, rising to a peak average current density of 22 mu A cm-2 after an average of 8 days
- in 2007 Rodriguez, et al. noted that there were commonalities among all mitochondrial-based disorders: 1. Lower cellular ATP 2. Proportionately more reliance on fermentative energy (i.e., glucose to lactic acid) 3. Greater production of reactive oxygen species (ROS)2
- In 2013, Vidali et al. showed that hair follicle aging (graying, hair loss, etc.) correlated with declining mitochondrial function,4 and by logical extension, lower energy levels
- a characteristic of low thyroid is the accumulation of mucopolysaccharides – combinations of proteins and sugars that deposit in the area between cells called the extracellular space.24 Evidence suggests that mucopolysaccharides, a hallmark of low thyroid, accumulate in the scalps of those men with pattern baldness and can act as a matrix for calcification.2
- During that time he removed the brains of about 80 cadavers and discovered a correlation between the blood vessel supply to the scalp and the quantity of hair present. In the cadavers with baldness, blood vessels that nourished hair had been “pinched” off by excessive calcification in the cavities (foramen) of the skull bones through which these blood vessels passed, thereby impairing circulation to the scalp. Dr. Hoelzel concluded that “hair tonics” or vitamins were not likely to restore blood circulation, through blood vessels that had practically become impeded by “solid ivory”.
- when researchers compared balding vs. non-balding scalps, they found that balding scalps produced finer, less pigmented hairs that were much less obviously vascularized. However, when they exposed balding scalp cultures to a supplemental blood supply, the growth rate of the balding scalp cultures increased by about 80 to 90 percent
- In another study, biopsies of balding regions of scalp were accompanied by vascular thrombosis, the formation of a blood clot inside a blood vessel that obstructs the flow of blood and nutrients to the hair follicle. In the final stages of pattern baldness the tissue surrounding the hair follicle gradually lost their capillaries until the skin appeared to be almost deprived of blood vessels
- reduced scalp oxygenation was noted by Goldman et al. in 1996, whose group stated that there was vascular insufficiency in regions of the scalp that lose hair during male pattern baldness
- Later on, Freund and Schwartz (2010) demonstrated that injections of botulinum toxin (i.e., botox) resulted in increased oxygen delivery to the frontal areas of the scalp, resulting in reduced hair loss and new hair growth among men with pattern baldness
- it was found that bald men had reduced bone mineral density when compared to men with hair3
- Progesterone acts as an anti-estrogen,4,5 supporting oxidative mitochondrial respiration and resolving the temporary growth-state induced by estrogen. However, if the factors needed to produce progesterone – such as thyroid hormone and vitamin A – are deficient, as they typically are in advanced age, estrogen can accumulate in the tissues to lower the metabolic rate and the efficiency by which energy is generated
- One of the clearest examples of how estrogen and progesterone affect hair growth is during pregnancy, when there is an increase in hair growth rate, hair diameter, and ratio of growing hairs to resting hairs6,7 – all of which result in a “lush head of hair.”8 In fact, in some cases pregnancy reverses “male-pattern” baldness in women.9 In contrast to the beneficial effects of pregnancy on hair growth, postpartum women routinely experience dramatic hair loss.10 But after giving birth, when progesterone levels fall sharply and estrogen and prolactin (the “lactation” or “molting hormone”) levels increase,11 the lush head of hair that had developed during pregnancy – when progesterone levels were soaring – disappears. In stark contrast to the hair-supportive conditions of pregnancy, menopausal conditions favor the development of “male-pattern baldness”.
- While professionals often proclaim menopause as an “estrogen deficiency”—as if there were no doubt about it— it is very clear, instead, that an elevated ratio of estrogen to progesterone is involved. Estrogen concentrations in tissues correlate positively with aging13,14,15 and with body fat levels.16,17 Because there is much misunderstanding, it is worth stating here that blood levels of estrogen do not necessarily reflect tissue concentrations of estrogen.18,19,20,21 Increased by estrogen,22,23 prolactin often becomes excessive around menopause,24 slows the metabolic rate,25 and inhibits the production of progesterone
- In one study, administering estrogen to rodents caused hair loss, while an antiestrogen drug renewed hair growth.29 In another experiment, dogs treated with large doses of estrogens lost their coats, which persisted even after the experiment ended.30 Similarly, prolactin treated rodents experience hair loss,31 and both estrogen and prolactin work together to initiate molting in birds.32
- Estrogen and prolactin both suppress thyroid function33 and interfere with the “efficient” production of energy,
- while progesterone opposes both hormones36 and supports respiration
- estrogen and prolactin were increased in those with pattern baldness
- lactating mothers are at very high risk for osteoporosis
- parathyroid hormone has also been shown to influence hair growth in animal experiments
- Because the exposure to cortisol is increased in age-related bone loss47,48 cortisol is thought to at least contribute to those conditions
- Because the exposure to cortisol is increased in patternbaldness,48 cortisol is thought to at least contribute to those conditions
- the anti-prolactin drug Bromocriptine has been successfully used to treat acne
- in a study of eight females with normal levels of androgens, Finasteride arrested the progression of hair loss for half of the women who used it
- serotonin increases the adaptive “stress” hormone, cortisol
- drugs that lower serotonin, serotonin-reuptake enhancers (SSREs), are effective agents for depression
- One study found that serotonin induced swelling in the mitochondria, and that adenosine triphosphate (ATP) reversed that swelling demonstrating that serotonin and ATP act in opposing directions in the cell.15 Another study found that serotonin interrupts oxidative mitochondrial respiration, promoting non-oxidative metabolism, increasing the formation of (the proinflammatory) lactic acid.1
- individuals with low thyroid tend to have higher levels of serotonin
- It, for instance, increases estrogen24,25,26 (and estrogen, in turn, increases serotonin)
- It, like estrogen, also increases prolactin
- it inhibits the formation of the pro-hair hormone progesterone
- Increased prolactin is a typical side effect of SSRIs
- Like estrogen and prolactin, serotonin causes bone loss and inhibits bone formation;31 on this basis, anti-serotonin drugs have been used to inhibit bone loss
- Endotoxin causes the release of serotonin
- Serotonin, in turn, causes inflammation in the intestines37 and appears in excess in inflammatory bowel diseases, such as irritable bowel syndrome (IBS), celiac disease, and Crohn’s disease
- Cortisol increases blood levels of endotoxin in a dose-dependent fashion
- endotoxin activates the enzyme that synthesizes new estrogen
- estrogen increases cortisol
- causes intestinal cells to become permeable
- In the long-term, free fatty acids have been referred to as a “toxic candidate” for the insulinsecreting pancreatic beta cells.20 In fact, it was found that chronic exposure to even moderate amounts of fatty acids dysregulates and impairs the functioning of the beta cells, even destroying them in severe cases.
- For example, experiments with animals showed that infusions of glucose increased the mass of beta cells by 250 percent over the course of 4 days.
- Lower levels of SHBG are associated with pattern baldness
- pattern baldness also seems to be associated with inadequate protein consumption to some degree.
- Tryptophan is associated with aging hair, and accumulates more so than other amino acid in graying hair
- in an experiment with college students, cholesterol levels went up before exams, and returned to normal shortly after the exam
- an infusion of fructose resulted in about 360 percent more hepatic glycogen than a glucose infusion
References
- Male hormone stimulation is prerequisite and an incitant in common baldness
- Persistent sexual side effects of finasteride for male pattern hair loss
- Association of androgenetic alopecia with metabolic syndrome in men: a community-based survey, Androgenetic alopecia and insulin resistance in young men, Sex hormone-binding globulin and risk of hyperglycemia in patients with androgenetic alopecia, Association of androgenetic alopecia and hypertension, [Male androgenetic alopecia and cardiovascular risk factors: A case-control study], Prevalence of polycystic ovaries in women with androgenic alopecia, Premature androgenic alopecia and insulin resistance. Male equivalent of polycystic ovary syndrome?, Male pattern baldness and coronary heart disease: the Physicians’ Health Study, Male pattern baldness and the risk of prostate cancer
- Trapped fingers and amputated finger tips in children, Measurement of electrical currents emerging during the regeneration of amputated finger tips in children
- Rodriguez, M.C., et al. Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerve. 2007 Feb;35(2):235-42.
- Hypothalamic-Pituitary-Thyroid Axis Hormones Stimulate Mitochondrial Function and Biogenesis in Human Hair Follicles
- Histochemistry of Dermis and Blood Vessels in Male Pattern Alopecia, Histochemistry of the acid mucopolysaccharides of skin in normal and in certain pathologic conditions
- Baldness and Calcification of The “Ivory Dome”
- A comparison of the culture and growth of dermal papilla cells from hair follicles from non-balding and balding (androgenetic alopecia) scalp
- Histochemistry of Dermis and Blood Vessels in Male Pattern Alopecia. Biopathology of Pattern alopecia
- Transcutaneous PO2 of the scalp in male pattern baldness: a new piece to the puzzle.
- Treatment of male pattern baldness with botulinum toxin: a pilot study.
- Premature graying, balding, and low bone mineral density in older women and men: the Rancho Bernardo study
- Estrogen replacement in ovariectomized rats results in physiologically significant levels of circulating progesterone, and co-administration of progesterone markedly reduces the circulating estrogen, The anti-aromatase effect of progesterone and of its natural metabolites 20alpha- and 5alpha-dihydroprogesterone in the MCF-7aro breast cancer cell line
- Physiological and biological skin changes in pregnancy, Scalp hair diameter increases during pregnancy, Morphological, Macromolecular Structure and Hair Growth. Chemical and Physical Behavior of Human Hair, Effect of pregnancy on the human hair cycle, Patterned androgenic alopecia in women
- Age-related changes in the female hormonal environment during reproductive life, Diminished function of the somatotropic axis in older reproductive-aged women, Age related changes in free plasma testosterone, dihydrotestosterone and oestradiol, Fat tissue: a steroid reservoir and site of steroid metabolism, The effects of age and body composition on circulating serum oestrogens and androstenedione after the menopause, Interrelations between plasma and tissue concentrations of 17 beta-oestradiol and progesterone during human pregnancy, Uptake and concentration of steroid hormones in mammary tissues, The endogenous concentration of estradiol and estrone in normal human postmenopausal endometrium, Tissue-specific synthesis and oxidative metabolism of estrogens, Hydrotestolactone lowers serum oestradiol and PRL levels in normal men: evidence of a role of oestradiol in prl secretion, Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation, The role of prolactin in the menopause, [Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress]
- An estrogen receptor pathway regulates the telogen-anagen hair follicle transition and influences epidermal cell proliferation, Inhibition of Hair Growth in Dogs Receiving Estrogens, Mind the (gender) gap: does prolactin exert gender and/or site-specific effects on the human hair follicle?
- [Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress], Biochemical changes in the reproductive cycle, [Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress]
- The anti-aromatase effect of progesterone and of its natural metabolites 20alpha- and 5alpha-dihydroprogesterone in the MCF-7aro breast cancer cell line, Basis of progesterone protection in spinal cord neurodegeneration
- Hormonal parameters in androgenetic hair loss in the male, [Hyperprolactinemia and hypophyseal hypothyroidism as cofactors in hirsutism and androgen-induced alopecia in women]
- Calcium and bone metabolism during pregnancy and lactation
- A topical parathyroid hormone/parathyroid hormone-related peptide receptor antagonist stimulates hair growth in mice
- Effects of major depression, aging and gender upon calculated diurnal free plasma cortisol concentrations: a re-evaluation study
- Hormonal basis of male and female androgenic alopecia: clinical relevance
- Bromocriptine treatment in patients with late onset acne and idiopathic hyperprolactinemia
- Frontal fibrosing alopecia: a survey in 16 patients
- Serotonin-induced stimulation of cortisol secretion from human adrenocortical tissue is mediated through activation of a serotonin4 receptor subtype, Regulation of 5-hydroxytryptamine metabolism in mouse brain by adrenal glucocorticoids, Serotonin acts centrally to affect renin release, and it promotes ACTH secretion
- A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression, Neurobiological and clinical effects of the antidepressant tianeptine
- Serotonin-induced swelling of rat liver mitochondria, Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists
- Thyroid hormones and the treatment of depression: an examination of basic hormonal actions in the mature mammalian brain, Hypothyroid-induced changes in autonomic control have a central serotonergic component, Thyroid hormone control of serotonin in developing rat brain
- Estrogen receptor beta regulates the expression of tryptophan-hydroxylase 2 mRNA within serotonergic neurons of the rat dorsal raphe nuclei, Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in distinct subregions of rat midbrain raphe nucleus: association between gene expression and anxiety behavior in the open field, Steroid regulation of tryptophan hydroxylase protein in the dorsal raphe of macaques, Serotonin in trigeminal ganglia of female rodents: relevance to menstrual migraine
- Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion
- Melatonin and serotonin regulate the release of insulin-like growth factor-I, oxytocin and progesterone by cultured human granulosa cells
- Pharmacological causes of hyperprolactinemia
- “Dopamine-dependent” side effects of selective serotonin reuptake inhibitors: a clinical review, Inhibition of gut-derived serotonin synthesis: a potential bone anabolic treatment, Efficacy of serotonin inhibition in mouse models of bone loss
- Serotonin release by bacterial endotoxin
- Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice, Serotonin, inflammation, and IBS: fitting the jigsaw together
- Dose-dependent effects of endotoxin on human sleep
- Effect of the aromatase inhibitor, 4 hydroxyandrostenedione, on the endotoxininduced changes in steroid hormones in male rats
- Estradiol stimulates cortisol production by adrenal cells in estrogen-dependent primary adrenocortical nodular dysplasia
- Estriol sensitizes rat Kupffer cells via gut-derived endotoxin
- The sensitivity of pancreatic beta-cells to mitochondrial injuries triggered by lipotoxicity and oxidative stress, Chronic exposure to free fatty acids or high glucose induces apoptosis in rat pancreatic islets: possible role of oxidative stress
- Enhanced beta-cell mass without increased proliferation following chronic mild glucose infusion
- Sex hormone-binding globulin and risk of hyperglycemia in patients with androgenetic alopecia, [Hormonal profile in men with premature androgenic alopecia]. , Sex hormone-binding globulin and saliva testosterone levels in men with androgenetic alopecia
- [Evaluation of the role of dietary intake in the occurrence of alopecia].
- Tryptophan in human hair: correlation with pigmentation
- Effects of periodic mental stress on serum cholesterol levels
- Liver and muscle glycogen in man after glucose and fructose infusion