"The role of mast cells in male-pattern baldness is unknown, but the large numbers often present is a striking feature." (Lattanand, 1975)
There are real differences between the frontal, parietal, temporal, and occipital regions of the scalp. Mainline baldness research typically attributes these differences to the area's sensitivity to androgens, but a recent shift has taken place, propelling hair loss research out of the dark ages towards an era of holism.
The shift began with Garza et al.'s landmark 2012 discovery that prostaglandin D2 inhibited hair growth and accumulated in the scalp's of balding men. Prostaglandin D2 is synthesized from the "essential" fatty acid, arachidonic acid, which is majorly produced from linoleic acid in the liver. This discovery reorients hair loss research in the direction of environmental factors rather than solely relying on genetic explanations.
I: Problematic Theories
The discovery that prostaglandin D2 is involved in baldness might also shed light on the somewhat mysterious horseshoe shape, or "baldness field" typical of pattern hair loss. But before we get too far, we should go over some (problematic) theories that attempt to explain the phenomenon:
#1: The Skull Expansion Theory of Pattern Hair Loss
The baldness field as a result of skull expansion was challenged as early as 1954. Changes in skull size, which generally occur throughout age in both sexes, doesn't appear to be associated with baldness. The idea has experienced somewhat of a resurgence with the 2009 paper, Big Head? Bald Head!, which I wrote about here. I appreciate the author's out-of-the-box view of pattern hair loss, but I don't think it shapes a realistic view of what's happening in the balding organism. Moreover, it tends to lead to aggressively stupid therapies (i.e., 'dissolving skull bone').
#2: The Ivory Dome Theory of Pattern Hair Loss
In the 2013 book, HAIR LIKE A FOX, I mentioned Frederick Hoelzel's famous Ivory Dome theory of pattern baldness. In short, Hoelzel observed that bald cadavers had calcified "solid ivory" scalps, while specimens with luxurious hair contained no such anomaly. Because pattern baldness is associated with hormones and signaling substances that negatively influence bone metabolism, I think it's likely that the intracellular accumulation of calcium is involved in the genesis of pattern baldness. However, whether that involves a "solid ivory" calcified scalp — I don't know. Is the spontaneous reversal of pattern baldness in cases of neonates, pregnancy, and male-to-female transgender due to the quick dissolution of a "solid ivory dome"? I think more research is needed.
#3: The Androgen Receptor Theory
The androgen receptor supposedly serves as the link between the inherited physiological state and the hormonal milieu needed for pattern baldness to manifest. If I understand the myth correctly, the balding area of the scalp, the frontoparietal region, has an increased amount of androgen receptors (or the androgen receptors are more "sensitive") than non-balding regions. The interaction between dihydrotestosterone (DHT) and the androgen receptor initiates a series of unfavorable events (that have yet to be identified) leading to hair loss. A minimal amount of effort reveals that the high levels of androgen receptors are found in people who aren't balding, and that the "sensitivity" argument apparently holds no water. Moreover, the "male" androgen receptor is activated by the adaptive "stress" hormone, prolactin,[8,9,10] which is increased by the so-called "female" hormone, estrogen. This fact, I think, completely invalidates the current model of androgen-driven inherited male-pattern baldness.
II: Transplanted Hairs
Another idea that needs to be addressed is that transplanted hairs from non-balding areas grow undisturbed in balding zones. If this were always true, it would support the near universal contention that the hair follicles are genetically preprogrammed to destruct at a certain time in an organism's life without aid from the environment.
In reality, transplanted hairs are affected by their environment and change overtime. In fact, the diameters of transplanted hairs tend to become significantly reduced.
In a strange experiment, balding hair follicles "quickly regenerated" and grew "as well as or better" after being grafted onto an immunodeficient mouse. Similarly, replacing the blood supply of balding hair follicles significantly increased their rate of growth and vitality. Perhaps there's 'something in the blood' that causes baldness, similar to what Alex Carrel noted in the 1930s with his "immortal" heart cells.
III: The Baldness Field
The galea is often the focus of pattern baldness research, labeling the temporal and occipital regions, "non-balding zones" or "androgen insensitive" areas. While the frontoparietal region of the scalp usually takes the hardest hit in pattern baldness (at least for males), all of the regions of the scalp are affected negatively.
In a 2002 paper, Dr. Gerard Seery warns that surgical intervention in the galea is, "difficult and bloody", and that the galea, when compared to other regions of the scalp, is particularly unforgiving to medical mistakes. Perhaps the increased number of complications involving the galea is due to the false belief that it has a "superabundant blood supply", which appears to be related to the genesis of baldness.
In 1980 Klemp et al., concluded that blood supply is reduced in bald tissues relative to controls. In 1990 Toshitani et al., demonstrated relatively reduced flow in the central scalp of male-pattern baldness patients. In 1996 Goldman found significant microvascular insufficiency in regions of the scalp that lose hair and an associated relative tissue hypoxia.
A reduction of peripheral blood flow isn't a random event; hormones and signaling substances direct the phenomenon. For example, in the 1970s W.D. Denckla found that the activation of the pituitary reduced the peripheral tissues (e.g., hands, head, feet, etc.) response to thyroid hormones, decreasing their oxygen consumption. The pituitary activates the parasympathetic nervous system and has a direct connection to mast cells throughout the body.
Mast cells are found in most tissues, but are particularly concentrated in locations that are in close contact with the external environment, such as skin, hair follicles, airways, and intestines. As early as 1975, it's been known that balding areas of the scalp contain an increased number of mast cells.
In 2014, is was reconfirmed that this area defined a "field" vulnerable to pattern hair loss.
The amount of mast cells in a given tissue is influenced by hormones and signaling substances involved in stress. For example, the number of mast cells in the uterus was shown to fluctuate during the estrous cycle. Ovariectomized mice, in which estradiol and progesterone are almost absent, have less mast cells compared to control, non-ovariectomized animals. Estrogen alone restored the number of uterine mast cells after ovariectomization, which was comparable to the levels observed in control mice.
In addition to increasing the number of mast cells in a given tissue, estrogen induces mast cell degranulation releasing inflammatory agents such as histamine, prostaglandins, serotonin, and nitric oxide. In contrast, carbon dioxide, which is produced under the direction of good thyroid function, inhibits mast cell degranulation.
The intensity of this inflammatory cascade is probably most influenced by the type of fat consumed over a lifetime (i.e., saturated vs. unsaturated). For example, the unsaturated fats are estrogenic, and work in the opposite direction of the thyroid-driven oxidative metabolism. Metabolic stress tends to increase estrogen, and in a vicious cycle, estrogen intensifies metabolic stress.[29,30]
Part of estrogen's ability to intensify the stress response is by activating enzymes that synthesize the pro-inflammatory prostaglandins.
IV: An Anti-Estrogenic Approach
The genesis of pattern baldness, and the subsequent realization of the baldness field, appears to stem from metabolic stress, or a reduced rate of metabolism. Because the rate of metabolism is influenced by so many hormones and signaling substances, I think the best way to increase metabolic functioning is to start with a solid nutritional foundation.
Nutritional approaches for baldness are sometimes met with laughter, which appears to be due to a strong cultural bias that only drugs with life altering side effects are useful for hair growth. I think this is a serious error, as a good diet, a thyroid supplement, and a little aspirin would appear to take care of many of the problems leading to the genesis of pattern baldness.
Rather than rehashing all of the dietary suggestions contained in HAIR LIKE A FOX, and this post, I'll mention a few that chronically tend to be absent in the diets of those who are experiencing hair issues.
#1: The Calcium to Phosphate Ratio
A high-calcium intake (in relation to dietary phosphate) limits the secretion of parathyroid hormone. An excess of parathyroid hormone causes mast cells to leak various inflammatory mediators associated with baldness. Phosphate comes packaged in all foods, but meeting the amount of phosphate in the diet with calcium can be difficult without the inclusion of milk, cheese, or supplemental eggshells. In addition to regularly including the calcium-rich foods in the diet, fructose can help balance the calcium/phosphate ratio.
#2: The Supplemental Foods
In my limited experience, it is common for those who are seeking to overcome hair loss to be taking many dietary supplements, but rarely include very nutritious foods in their diet such as ruminant liver, oysters, and egg yolks. Baldness is associated with various nutritional deficiencies such as copper, zinc, and possibly other nutrients. I think including a portion of beef liver and oysters each week, along with eggs everyday, is a safer, cheaper, and a less confusing way to obtain nutrients that support general resistance to stress.
#3: The Resting Temperature and Pulse
The rate of metabolism is represented by the cyclical rise and fall of the body temperature and pulse rate. Thyroid hormone tends to increase the temperature, while estrogen, serotonin, and prolactin tend to reduce it.[39,40] Obtaining full nutrition while increasing the resting temperature and pulse rate, I think, is a good strategy for combatting the complex biochemical web of unfavorable events that lead to hair aging.
- 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.
- Martin, C.R. Endocrine Physiology. 1985. “All members of this group are synthesized from ‘polyunsaturated’ fatty acids that must be supplied by the diet. From a quantitative standpoint, arachidonic acid is the major presurosor.”
“Meats and peanuts contain small amounts [of arachidonic acid], but the liver forms most of it from linoleic acid. Arachidonic acid is the presurosor of the prostaglandins with two double bonds, and of the several other biologically potent substances.”
- Garn, S.M., et al. Scalp Thickness and The Fat-Loss Theory of Balding. AMA Arch Derm Syphilol. 1954;70(5):601-608.
- Taylor, P.J. Big head? Bald head! Skull expansion: alternative model for the primary mechanism of AGA. Med Hypotheses. 2009 Jan;72(1):23-8.
- Hoelzel, F. Baldness and Calcification of The “Ivory Dome”. JAMA. 1942;119(12):968.
- Stenn, S.S. The Molecular and Structural Biology of Hair. Ann N Y Acad Sci. 1991. “However, the androgen receptor may not be the sole determinant of androgen action on scalp hair follicles, as a high level of receptor was found in a dermal papilla culture from the vertex of a nonbald man of 73 years.”
- Prins, G.S. Prolactin influence on cytosol and nuclear androgen receptors in the ventral, dorsal, and lateral lobes of the rat prostate. Endocrinology. 1987 Apr;120(4):1457-64. “These findings suggest that PRL promotes lateral prostatic growth by increasing nuclear androgen receptor levels in that tissue and, thus, optimizes its response to circulating testosterone.”
- Odoma, S. et al. Evidence for the association between blood prolactin and androgen receptors in BPH. J Urol. 1985 Apr;133(4):717-20. “The results suggest that plasma prolactin may be involved in the regulation of androgen receptor content in the benign prostate.”
- Strum, S.S. Is There A Correct Way to Treat Prostate Cancer? “Prolactin is a known stimulator of androgen receptors and is also associated with an adverse clinical course in men with prostate cancer. Because we now have new drugs that have an anti-prolactin effect, we find it important that we assess the prolactin level as a baseline and also at times when the clinical course is changing for the worse. It is also conceivable that we should monitor and perhaps treat elevated prolactin levels of men on anti-cancer therapies that stimulate prolactin, e.g. estrogens, and Emcyt.” Prostate Cancer Research Institute (1998)
- Kim, J.Y., et al. Characteristics of nonbalding scalp zones of androgenetic alopecia in East Asians. Clin Exp Dermatol. 2015 Apr;40(3):279-85. “The so-called ‘nonbalding zones’ of the scalp, which comprise the occipitotemporal regions, are typically unaffected by dihydrotestosterone and are androgen- insensitive. Therefore, hairs on those anatomical areas remain, despite the progression of AGA. However, clinically, hairs on nonbalding zones seem to be reduced in number or width, and the character of transplanted hairs taken from those sites can change over time.”
- Seery, G.E. Surgical anatomy of the scalp. Dermatol Surg. 2002 Jul;28(7):581-7. “More than 3000 scalp operations, done personally, were reviewed. These covered the entire spectrum of plastic and reconstructive surgery and hair restoration procedures including more than 700 clinical surgical investigative procedures with pericranial flaps, subgaleal and subperiosteal scalp reductions, and deep plane fixation procedures.” “It may also be a factor in explaining why the diameters of transplanted hair become significantly reduced in the posttransplant state.”
- Krajcik, R.A., et al. Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice. J Am Acad Dermatol. 2003 May;48(5):752-9. “This report shows that miniaturized hair follicles of pattern alopecia can quickly regenerate once removed from the human scalp and can grow as well as or better than terminal follicles from the same individual.”
- Randall, V.A., et al. A comparison of the culture and growth of dermal papilla cells from hair follicles from non-balding and balding (androgenetic alopecia) scalp. Br J Dermatol. 1996 Mar;134(3):437-44. “Balding dermal papillae were much smaller than non-balding ones and grew much less well under normal growth conditions. Supplementing the medium with human serum, rather than fetal caH serum, increased both the yield of established cultures and the number and health of the dermal papilla cells produced. Non-balding cells also grew faster in human serum. Balding cells retained the normal fibroblastic shape and aggregative behaviour of dermal papilla cells, but always grew less well than non-balding cells.” “Balding-region follicles produced finer, and less pigmented. hairs and were much less obviously vascularized” “When primary papilla cultures were established in medium supplemented with 20% human serum, a greater success rate was achieved. with 80-90%. of both non-balding and balding samples yielding established cell lines.”
- Carrel, A. Man, The Unknown. 1935. “The rhythm of physiological time depends on the relations between the tissues and their medium. It varies according to the volume, the metabolic activity, the nature of the cell colony, and the quantity and the chemical composition of the fluid and gaseous media. The technique used in the preparation of a culture accounts for the rhythm of life of such culture. For example, a fragment of heart fed with a single drop of plasma in the confined atmosphere of a hollow slide, and another one immersed in a flask containing a large volume of nutritive fluids and gases, have quite different fates. The rate of accumulation of the waste products in the medium, and the nature of these products, determine the characteristics of the duration of the tissues. When the composition of the medium is maintained constant, the cell colonies remain indefinitely in the same state of activity. They record time by quantitative, and not by qualitative, changes. If, by an appropriate technique, their volume is prevented from increasing, they never grow old. Colonies obtained from a heart fragment removed in January, 1912, from a chick embryo, are growing as actively today as twenty-three years ago. In fact, they are immortal.”
- Seery, G.E. Surgical anatomy of the scalp. Dermatol Surg. 2002 Jul;28(7):581-7. “The belief that scalp has a superabundant blood supply and consequently is very forgiving of surgical indiscretions may need to be reconsidered. This has particular relevance to hair restoration surgery.” “The following description is based on more than 700 pericranial dissections I have per- formed.” “Its surface is densely adherent to the subcutaneous tissues, thus making dissection in this plane difficult and bloody.” “The galea is significantly resistant to stretching and is believed by some surgeons to be the main factor standing in the way of meaningful scalp resection.”
- Klemp, P., et al. Subcutaneous blood flow in early male pattern baldness. J Invest Dermatol. 1989 May;92(5):725-6. “A reduced nutritive blood flow to the hair follicles might be a significant event in the pathogenesis of early male pattern baldness.”
- Toshitani S., et al. A new apparatus for hair growth in male pattern baldness. J Dermatol 1990;17:240. “An investigation into the basis for the hair regrowth caused by this apparatus was directed toward the changes in hemodynamics and skin temperature of the scalp. During and after use of this apparatus, subjects exhibited an increase both in the cutaneous blood flow rate (as determined by laser Doppler flowmetry) and in the cutaneous temperature (as determined by thermography).”
- 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.
- Denckla, W.D. 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.”
- Lattanand, A. and Johnson, W.C. Male pattern alopecia a histopathologic and histochemical study. J Cutan Pathol. 1975;2(2):58-70. “The role of mast cells in male-pattern baldness is unknown, but the large numbers often present is a striking feature.”
- Larson, A.R., et al. A prostaglandin D-synthase-positive mast cell gradient characterizes scalp patterning. J Cutan Pathol. 2014 Apr;41(4):364-9. “These data indicate that scalp is spatially programmed via mast cell prostaglandin D-synthase distribution in a manner reminiscent of the pattern seen in androgenetic alopecia.”
- Aydin, Y., et al. Ovarian, uterine and brain mast cells in female rats: cyclic changes and contribution to tissue histamine. Comp Biochem Physiol A Mol Integr Physiol. 1998 Jun;120(2):255-62. “The number, degranulation pattern and staining characteristics of mast cells changed synchronously in rat ovarian, uterine and brain tissues during the estrus cycle.”
- Jensen, F., et al. Estradiol and progesterone regulate the migration of mast cells from the periphery to the uterus and induce their maturation and degranulation. PLoS One. 2010 Dec 22;5(12):e14409. “The number of MCs in the uterus has been shown to fluctuate during menstrual cycle in human and estrus cycle in rat and mouse indicating a hormonal influence on their recruitment from the periphery to the uterus.“ “We propose that estradiol and progesterone modulate the migration of MCs from the periphery to the uterus and their degranulation, which may prepare the uterus for implantation.”
- Arck, P.C., et al. Neuroimmunology of stress: skin takes center stage. J Invest Dermatol. 2006 Aug;126(8):1697-704. “Thus, skin mast cells not only are highly sensitive to modulation of their activities by classical stress hormones but also generate key stress hormones (at least CRH) themselves.”
- Strider, J.W., et al. Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels. Allergy. 2011 Mar;66(3):341-50. "Results from this study provide the first evidence of a unique regulatory mechanism by which CO₂ inhibits mast cell degranulation and histamine release by repressing stimulated increases in intracellular calcium. Thus, our data provide a plausible explanation for the reported therapeutic benefit of noninhaled intranasal delivery of 100% CO₂ to treat allergic rhinitis."
- Bruning, P.F., and Bonfrèr, J.M. Free fatty acid concentrations correlated with the available fraction of estradiol in human plasma. Cancer Res. 1986 May;46(5):2606-9. “A physiological in vivo increase of plasma free fatty acid concentration after an overnight fast was found to be accompanied by a rise of the non-protein bound estradiol fraction.” "...was markedly dissociated by oleate and even more by linoleate, linolenate, or arachidonate." “These results suggest that physiological diurnal elevations in plasma free fatty acids which are amplified by high fat consumption, obesity, and stress may imply major proportional increases of available estradiol, exerting a promotional effect on breast and endometrial cancer over the years.”
- Lee, H.J., et al. Selective remodeling of cardiolipin fatty acids in the aged rat heart. Lipids Health Dis. 2006; 5: 2. “The concentration (nmol/g) of linoleic acid was decreased in 24 month old rats (3965 ± 617, mean ± SD) vs 4 month old rats (5525 ± 656), while the concentrations of arachidonic and docosahexaenoic acid were increased in 24 month old rats (79 ± 9 vs 178 ± 27 and 104 ± 16 vs 307 ± 68 for arachidonic and docosahexaenoic acids, 4 months vs 24 months, respectively). Similar changes were not observed in ethanol amine glycerophospholipids or plasma unesterified fatty acids, suggesting specificity of these effects to cardiolipin.” “These results demonstrate that cardiolipin remodeling occurs with aging, specifically an increase in highly unsaturated fatty acids.”
- Shors, T.J., et al. Acute stress persistently enhances estrogen levels in the female rat. Stress. 1999 Dec;3(2):163-71. “These results indicate that exposure to a relatively acute stressful event immediately and persistently enhances serum estradiol and are discussed in the context of reports that exposure to the same stressors immediately and persistently impairs associative learning in the female rat.“
- 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 pro gestational steroids may be such as to interfere with the biochemical pattern required for support of this anaerobic environment.”
- Nagy, P., and Csaba, I.F. [Action of oestrogens on in vitro metabolism of trophoblast from human early pregnancy (author’s transl)]. Zentralbl Gynakol. 1982;104(2):111-6. “Warburg’s manometric method was used to check the action of oestrone, oestradiol, and oestriol on aerobic and anaerobic glycolysis of placental respiration. Oestrogen concentrations of 10(-4) M were found to reduce oxygen consumption and to increase aerobic glycolysis. Such reduction of oxygen consumption was most strongly pronounced in connection with oestradiol, while the strongest rise in aerobic glycolysis took place in the wake of oestradiol and oestrone. Oestrogen action upon anaerobic glycolysis was variable, with the latter remaining unchanged by oestradiol, reduced in response to oestriol, and slightly increased by oestrone.“
- Thomas, W., et al. Estrogen induces phospholipase A2 activation through ERK1/2 to mobilize intracellular calcium in MCF-7 cells. Steroids. 2006 Mar;71(3):256-65. Epub 2005 Dec 22. "Here we show, for the first time, that PLA(2) and the eicosanoid biosynthetic pathway are involved in the 17beta-estradiol induced rapid calcium responses of breast cancer cells."
- Martin, C.R. Endocrine Physiology. 1985. “It is universally agreed that hypercalcemia leads to accelerated degradation of PTH within the parathyroid cells.”
- Tsakolos, N.D., et al. Induction of mast cell secretion by parathormone. Biochem Pharmacol. 1983 Jan 15;32(2):355-60. “Release of serotonin and histamine was demonstrated with 25 units/ml PTH or higher.” “These results demonstrate that elevated levels of PTH can induce mast cell secretion in vitro and in vivo and suggest a possible role for mast cells in the pathophysiology of non-allergic disease states.”
- Kapur, S. A medical hypothesis: phosphorus balance and prostate cancer. Cancer Invest. 2000;18(7):664-9. “…dietary fructose reduces plasma phosphate levels by 30 to 50%…”
- Skalnaya, M.G. Copper Deficiency a New Reason For Androgenic Alopecia? 2014. “The exception was the concentration of copper (Cu) which was statistically significant differences between men and women suffering from AA and matched control (Table 1).” “The key disorder was decreased Cu level in frontal zones of scalp hair and serum.”
- Kil, M.S., et al. Analysis of Serum Zinc and Copper Concentrations in Hair Loss. Ann Dermatol. 2013 Nov; 25(4): 405–409. “The data led to the hypothesis of zinc metabolism disturbances playing a key role in hair loss, especially AA and TE, whereas the effect of copper on hair growth and shedding cycles still needs more study.”
- Landsberg, L., et al. Is obesity associated with lower body temperatures? Core temperature: a forgotten variable in energy balance. Metabolism. 2009 Jun;58(6):871-6. “Changes in body temperature are associated with significant changes in metabolic rate.” “Resting metabolic rate is largely regulated by thyroid hormones,” “Resting (or “basal”) metabolic rate (RMR) accounts for approximately 80%of energy output.” “Physical activity (exercise) accounts for about 10% in truly sedentary humans” “This metabolic energy required for homeothermy is thyroid dependent and apparently generated principally in mitochondria throughout the body of warm-blooded animals.” “Hibernation and the lesser state of shallow torpor wherein the temperature falls at night are energy-saving adaptations used by a variety of mammals” “A decrease in body temperature, in fact, occurs at night in relation to the sleep cycle in human populations [58,59]. A fall in body temperature occurs during starvation, as noted above, and in hypoglycemia, an acute state of energy deprivation.” ”These 2 components address the 2 main physiologic imperatives of starvation: energy conservation and protein preservation. A decrease in metabolic rate would lead to more efficient storage of calories as fat, thereby prolonging survival during famine; during periods of abundance and in the face of dietary excess, this trait would predispose to obesity. Resistance to the action of insulin would divert glucose from skeletal muscle, which can use fat-derived substrates, to the brain, an organ almost entirely obligated to the use of glucose. In the presence of famine, insulin resistance would spare muscle breakdown by lessening the need for gluconeogenesis from protein; in the face of an abundant food supply, however, and in association with dietary excess, insulin resistance would predispose to type 2 diabetes mellitus.”
- The Merck Manual Seventh Edition. 1940. “Hypothyroidism. Gradual onset of apathy, gain in weight, and development of nonpittng edema, especially of hands, feet and face. Skin dry and scaly. Hair becomes brittle and thin, nails rough, striated and break easily. There are lassitude, fatiguability, drowsiness, imperfect cerebration, even psychosis; poor appetite and constipation; pulse slow, blood pressure low, temperature subnormal; menstruation irregular; may cease or become excessive. Anemia in majority of cases.” “Causes: A disease in middle life, 6 times more common in women than in men, especially liable to occur with menstrual disturbances. Diagnoses: Gradual onset of apathy, gain in weight, and development of nonpitting edema, especially of hands, feet and face (“full moon-like” face and coarse features). Skin dry and scaly (scales best seen in stockings. Hair becomes brittle and thin, nails rough, striated and break easily. There are lassitude, fatiguability, drowsiness, imperfect cerebration, even psychosis; poor appetite and constipation; pulse slow, blood pressure low, temperature subnormal; menstruation irregular; may cease or become excessive. Anemia in majority of cases. Tests: Basal metabolism low, hypercholesteremia, alimentary tolerance for dextrose greatly increased, diminished sensitivity to epinephrine and pilocarpine. Therapy: The administration of desiccated thyroid which may have to be continued throughout life is best divided into two periods: 1. Initial Dose: One usually may commence with 1 grain of thyroid 3 times a day; and increased dose by 1 grain a week until 3 grains is taken three times a day or until there is feeling of warmth, increased pulse rate, quicker mental reaction. These symptoms are followed by elevation of temperature, sharp loss of body weight, sweating and increased metabolic rate… Exercise should be very constricted until improvement is well advanced.”
- Books, E.M., et al. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J Appl Physiol. 1997 Aug;83(2):477-84.
- Drago, F., and Amir, S. Effects of hyperprolactinaemia on core temperature of the rat. Brain Res Bull. 1984 Apr;12(4):355-8.