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Endocrinology and alcohol 

Endocrinology and alcohol
Chapter:
Endocrinology and alcohol
Author(s):

Margit G. Proescholdt

and Marc Walter

DOI:
10.1093/med/9780199235292.003.2254
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date: 26 November 2020

Introduction

Alcohol has widespread effects on multiple organs, including the endocrine organs, potentially impairing endocrine function and affecting the entire endocrine milieu. Endocrine impairment may be observed with acute alcohol ingestion, excessive chronic alcohol consumption, and during alcohol withdrawal. Whereas many effects of alcohol on the endocrine organs are reversible following cessation of alcohol consumption, some changes may extend into abstinence. Importantly, endocrine dysfunction observed in alcoholism, is no longer considered to simply result from hepatic failure or chronic malnutrition, but, at least partially, from direct, toxic actions of alcohol on the endocrine organs themselves. In addition, there is increasing evidence that the endocrine system itself may play a crucial role in the pathogenesis of addictive behaviour.

Ethanol and its metabolite acetaldehyde directly affect cell membranes and influences intracellular metabolism. Indirect effects include stress, nausea, and vomiting during acute intoxication and withdrawal. Whereas the list of alcohol-induced endocrine dysfunction is long, scientific and epidemiological evidence is frequently controversial. Controversies may result from the highly heterogenic group of alcohol-dependent individuals regarding dose and duration of alcohol consumption, periods of abstinence, age, gender, nutritional status, cigarette smoking, use of other drugs, presence of other diseases, particularly liver disease, and the complexity of endocrine regulation in general.

Hypothalamic–pituitary–adrenal (HPA) axis and alcohol

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis have long been reported in alcohol-dependent patients. In healthy volunteers alcohol effects on the HPA axis are dose-dependent. Alcohol amounts corresponding to social drinking attenuate HPA axis activity, whereas alcohol-induced HPA stimulation can only be seen if nausea occurs which markedly triggers vasopressin (AVP) secretion, thereby stimulating adrenocorticotropic hormone (ACTH). By contrast, chronic alcohol consumption may result in increased serum cortisol levels (Table 2.6.4.1). Plasma concentrations of ACTH may be normal or increased, and urinary excretion of free cortisol is frequently increased. Furthermore, alcohol-dependent patients show a persisting cortisol hyporeactivity to a wide range of stressors (1).

Table 2.6.4.1 Hypothalamic–pituitary–adrenal axis and alcoholism

Clinical findings

Pseudo-Cushing syndrome: rare

Laboratory findings

Serum cortisol: normal or increased

Adrenocorticotropic hormone: normal or increased

Urinary free cortisol: increased

Cortisol hyporeactivity to various stressors

CRF system

Suggested key role in facilitating and maintaining substance use disorders

Rarely, alcohol-dependent patients develop pseudo-Cushing’s syndrome, which is indistinguishable from true Cushing’s syndrome, but may present with fewer biochemical alterations and fewer clinical symptoms. Hormonal testing shows an increased secretion of cortisol which is not suppressed by the overnight dexamethasone test. Importantly, both the physical and the hormonal abnormalities improve after discontinuation of alcohol use, which is why abstention from alcohol not only is curative but also an important diagnostic tool.

Acute alcohol withdrawal results in immediate increases of circulating plasma levels of cortisol and ACTH, disruption of the normal diurnal cortisol secretion pattern, and a blunted response of ACTH to various stressors including intravenous (i.v.) corticotropin-releasing factor (CRF). Accordingly, it has been suggested that enhanced ACTH and cortisol, as well as extrahypothalamic CRF levels (animal studies), contribute to the stressful and anxiogenic state observed during alcohol withdrawal (2). As the withdrawal syndrome wanes, cortisol and ACTH levels, as well as the diurnal secretion pattern normalize. However, HPA regulation may not be completely normal even after the diurnal pattern has recovered, as shown by deficient cortisol responses to HPA stimulation by CRF in abstinent alcohol-dependent patients. Furthermore, low baseline serum cortisol levels, and a blunted cortisol stress response were shown to correlate with increased craving for alcohol, and an increased risk for relapse, respectively (2). In abstinent alcohol-dependent patients (day 40), cortisol levels in the cerebrospinal fluid were shown to decrease compared with normal controls, and relapsers showed higher levels than abstainers (3).

In addition, there is increasing evidence that the HPA axis—with particular emphasis on the CRF system—plays a key role in facilitating and maintaining substance use disorders, and may therefore qualify as a major target for its treatment. To date the mechanisms by which alcohol interferes with the HPA axis are not fully understood, and include direct effects of alcohol on all levels of the HPA axis, as well as genetic, and environmental factors (2, 4).

Male gonadal function and alcohol

It is well known that chronic and excessive alcohol consumption eventually results in gonadal failure (hypogonadism). Although overt alcohol-induced hypogonadism is more frequent in alcohol-dependent men with advanced liver disease, gonadal dysfunction is also observed in the absence of liver cirrhosis. Hypogonadism is manifested by testicular atrophy, infertility, loss of libido, and impotence. In particular, seminiferous tubular atrophy, and marked abnormal seminal determinations are frequent findings in alcohol-dependent men independent of liver disease (5). Likewise, sexual disorders are frequently reported, with prevalence estimates ranging from 8% to 58%. In the absence of significant hepatic or gonadal failure, abstention may result in the recovery of normal sexual function even after a history of prolonged and severe alcohol abuse (6), although persistent sexual dysfunction has been reported as well.

Feminization, by contrast, is distinct from hypogonadism, and is manifested by gynaecomastia, female body habitus changes, spider angiomata, palmar erythema, and changes in body hair patterns. Feminization occurs later in the course of chronic alcohol disease, and is seen only occasionally in the absence of liver disease. Clinical reports on sex hormone profiles are somewhat inconclusive. The most common findings are shown in Table 2.6.4.2 (7, 8).

Table 2.6.4.2 Hypothalamic–pituitary–gonadotropic axis in men and alcoholism

Clinical findings

Hypogonadism

Feminizationa

Laboratory findings

Testosterone: normal, decreaseda

Free testosterone: normal, decreased

SHBG: increased

FAI: normal, decreased

FSH: normal, increased

LH: normal, increased

Androstendione: normal, increased

Oestradiol: normal, increased

* Particularly in patients with advanced liver disease. FAI, free androgen index; FSH, follicle-stimulating hormone; LH, luteinizing hormone; SHBG, sex hormone-binding globulin.

In general, acute administration of alcohol to healthy male volunteers results in decreased testosterone levels. Decreased testosterone levels are also common in alcoholic liver disease. By contrast, in the absence of liver impairment, total testosterone levels are mostly within the normal range. Yet, concentrations of the sex hormone-binding globulin (SHBG) are usually increased in actively drinking men. Accordingly, some studies report a reduced free androgen index (FAI: total testosterone/SHBG), indicating a reduced free-to-total plasma testosterone ratio, and thus a condition of relative hypoandrogenism. Concentrations of the gonadotropins (luteinizing hormone and follicle-stimulating hormone (FSH)) are reported normal or increased when compared to healthy individuals. In addition, studies have found inadequately normal or raised luteinizing hormone concentrations in the presence of reduced or increased testosterone levels, respectively, indicating a disturbance of the testosterone-mediated adenohypophyseal feedback mechanism (9). During withdrawal, testosterone levels were shown to increase (8, 10) while concentrations of SHBG and oestradiol decrease. However, sustained increases in serum testosterone in the presence of inadequately raised luteinizing hormone concentrations were still observed up to 4 months after cessation of drinking (10).

Although the underlying mechanisms have not been completely identified, alcohol-induced hypogonadism is attributed to a direct (toxic) alcohol-induced primary gonadal injury and to an alcohol-associated hypothalamic pituitary dysfunction. Feminization, by contrast, may result from the combined effects of altered enterohepatic circulation of biliary excreted steroids as a result of portal hypertension and liver disease, and conversion of weak adrenal androgens to oestrogens.

Female gonadal function and alcohol

Premenopausal women

Chronic heavy consumption of alcohol can contribute to a multitude of reproductive disorders. These include amenorrhoea, anovulation, menstrual cycle irregularities, loss of libido, early menopause, and increased risk of spontaneous abortions. These dysfunctions can be caused by alcohol’s interfering directly with the hormonal regulation of the reproductive system or indirectly through other disorders associated with alcohol consumption, such as liver disease, pancreatic disease, malnutrition, or fetal abnormalities. Prospective and well-designed studies on the effects of alcohol on female hormone levels in premenopausal alcohol-dependent women are sparse, and data available so far are still inconclusive. In detail, oestradiol levels are reported increased, normal, or reduced. Progesterone levels are more consistently reported reduced, especially during the luteal phase. Test-osterone levels are reported increased or decreased. Gonadotropins (luteinizing hormone and FSH) are reported unchanged or decreased (11).

Acute alcohol ingestion is shown to substantially increase plasma testosterone levels, whereas reports on oestradiol (increased or normal) and progesterone (decreased or normal) levels are less conclusive (12, 13).

In ‘modest’ alcohol consumption, studies indicate an alcohol-induced rise in oestrogen levels, however, the positive (for example, protection against osteoporosis and cardiovascular disease) and/or negative (for example, breast cancer) implications of these findings on female health need further evaluation. Further studies are also needed to clarify the effects of modest alcohol consumption on the onset of menopause (suggested to be delayed) and fecundity (suggested to be unaltered or reduced). In the specific case of reproductive health, binge drinking may be most detrimental at certain times, namely puberty, the cyclical selection of follicles for maturation, ovulation, and the implantation and subsequent survival of the blastocyst (12). Furthermore, studies indicate that alcohol consumption during early adolescence may delay puberty and adversely affect the maturation of the female reproductive system. The latter findings clearly emphasize the risks of underage drinking and the importance of its prevention.

Postmenopausal women

In postmenopausal women with alcohol-induced cirrhosis, oestradiol and prolactin levels are significantly increased, and levels of testosterone, luteinizing hormone, and FSH are decreased compared to abstaining postmenopausal women or postmenopausal women with moderate alcohol consumption. Whereas the decreased levels of luteinizing hormone and FSH may result from the increased oestradiol levels, the decreases in luteinizing hormone and FSH may also reflect a more subtle alcohol-induced central defect at the level of the hypothalamus and pituitary (14). In postmenopausal women with ‘moderate’ alcohol consumption (0.1 to 28 drinks/week), oestradiol levels are increased, and testosterone levels are decreased, compared to abstaining postmenopausal women. Luteinizing hormone, FSH, and prolactin levels do not differ between these two groups. Furthermore, moderate alcohol consumption (no more than one drink per day) is being suggested to increase oestradiol levels in postmenopausal women with respective positive (for example, protection from osteoporosis and cardiovascular disease) and negative (increased risk for breast cancer) implications. However, so far, a firm relationship between moderate alcohol consumption and oestrogen levels in postmenopausal women has not been established (15). By contrast, effects of alcohol on oestrogen levels in postmenopausal women exposed to oestrogen replacement therapy (ERT) are more consistent, but variable. In oral ERT, alcohol administration was shown to result in robust increases in blood oestradiol levels. Increased circulating oestradiol levels, however, may increase the risk of breast cancer in postmenopausal women (15).

Alcohol and breast cancer

Several studies have noted an association between alcohol and breast cancer, and risk estimates are shown in Table 2.6.4.3. Despite the well-established fact that breast cancer is multifactorial in nature, and despite a relatively moderate excess risk, the high incidence of breast cancer results in more women with breast cancer attributable to alcohol than for any other type of cancer (16).

Table 2.6.4.3 Relative risk for major chronic disease categories, by gender and average drinking category

Drinking categorya

Disease

I

II

III

Hypertensive disease

Females

1.40

2.0

2.0

Males

1.40

2.0

4.10

Breast cancer

1.14

1.41

1.59

Under 45 years of age

1.15

1.41

1.46

45 years and over

1.14

1.38

1.62

Diabetes mellitus

Females

0.92

0.87

1.13

Males

1.0

0.57

0.73

a Drinking category: females: I, 0–19,99; II, 20–39.99; III, 40 or more g pure alcohol per day; males: I, 0–39.99; II, 40–59.99; III, 60 or more g pure alcohol per day.

Modified from Rehm J, Gmel G, Sempos CT, Trevisan M. Alcohol-related morbidity and mortality. Alcohol Res Health, 2003; 27: 39–51 (17).

The exact mechanisms by which alcohol causes breast cancer are still unknown. Several hypotheses exist, and include perturbation of oestrogen metabolism and response, induction of mutagenesis by acetaldehyde derived from oxidation of ethanol by alcohol dehydrogenase, stimulation of oxidative damage through ethanol metabolism, and/or affection of folate and one-carbon metabolism pathways. By contrast, alcohol does not seem to increase the risk of endometrial cancer. A possible protective effect of alcohol on the risk of ovarian cancer needs further investigation (16).

Hypothalamic–pituitary–thyroid (HPT) axis and alcohol

In alcohol-dependent patients, thyroid dysfunction is a frequent finding. However, consensus on clinical relevance and mechanisms has not been achieved. Thyroid dysfunction is particularly evident during chronic alcohol consumption and early abstinence (less than 3 weeks), and usually normalizes during abstinence. In individuals, where thyroid dysfunction persists into abstinence, other nonalcohol-related thyroid diseases should be excluded (e.g. auto-immune thyroid disease). In patients with pre-existing hyperthyroidism, acute alcohol intoxication may promote the manifestation of a thyrotoxic crisis, warranting immediate analysis of thyroid hormones and adequate medical treatment. Furthermore, alcohol-associated HPT axis dysfunction has been associated with relapse prediction, the severity of withdrawal symptoms, and considered a trait marker for the risk to develop alcohol dependence, the latter being controversial.

Regarding thyroid hormones (Table 2.6.4.4), the most consistent findings include a reduction in total thyroxin (T4), total (T3) and free triiodothyronine (fT3) concentrations during early abstinence, normal thyroid-stimulating hormone (TSH) levels, and a blunted TSH response following administration of thyrotropin-releasing hormone (TRH, TRH test). Reductions in peripheral thyroid hormones and TRH blunting are particularly evident during withdrawal. During abstinence, peripheral hormones usually normalize, whereas TRH blunting may still be observed after several weeks thereafter (18). Independent of liver disease, thyroid volumes are significantly decreased in alcohol-dependent patients, indicating a direct toxic and dose-dependent effect of alcohol on the thyroid gland (19).

Table 2.6.4.4 Thyroid gland and alcoholism

Clinical findings

Usually absence of overt clinical signs of hypothyroidism

Thyroid volume reduced

Laboratory findings

Basal thyroid-stimulating hormone: usually normal

Free or total T3: may be reduced

Free or total T4: usually normal

Thyrotropin-releasing hormone test: frequently blunted

The exact mechanisms by which alcohol causes dysfunction of the HPT axis are still unknown. However, evidence suggests direct toxic effects of alcohol on the thyroid gland and its metabolism, as well as central effects at the level of the hypothalamus and/or pituitary (18).

Water and electrolyte balance and alcohol

The main regulator of blood and urine osmolality, the antidiuretic hormone arginine vasopressin (AVP), is profoundly altered by alcohol. In alcohol-naïve individuals, mild to moderate alcohol ingestion leads to a dose-dependent suppression of AVP resulting in water diuresis. After cessation of alcohol intake, AVP suppression and diuresis resolve resulting in a normalization of water balance and plasma osmolality (Table 2.6.4.5). By contrast, single large doses of alcohol increase plasma AVP levels. When alcohol concentrations are kept steady in normal volunteers, additional doses of alcohol produce progressively smaller and eventually negligible diuretic responses.

Table 2.6.4.5 Effects of alcohol on water and sodium homoeostasis

Ascending plasma alcohol concentrations

Plasma AVP: decrease

Water diuresis: increase

Plasma osmolality: increase

Descending plasma alcohol concentrations

AVP: increase

Voluntary fluid intake: increase

Water diuresis: decrease

Plasma osmolality: normalization

Chronic alcohol intake

Possible overhydration

Acute alcohol withdrawal

Plasma AVP: increase

Possible overhydration

After alcohol withdrawal

Plasma AVP: decrease

Water, sodium, chloride excretion: increase

Body volumes: normalization

AVP, argenine vasopressin.

Modified from Vamvakas S, Teschner M, Bahner U, Heidland A. Alcohol abuse: potential role in electrolyte disturbances and kidney diseases Clin Nephrol, 1998; 49: 205–13 (20).

Chronic alcohol ingestion does no longer suppress baseline AVP levels, but rather results in the development of tolerance to the effects of alcohol. Clinical studies measuring AVP levels in alcohol-dependent patients, however, show conflicting results with elevated, normal, and decreased AVP levels. Furthermore, chronic alcohol consumption may be associated with isosmotic overhydration although dehydration has been suggested as well (21). In particular, persons who consume large quantities of beer with low total solute intake (sodium content of beer: less than 2 mmol/l) are at risk to develop life-threatening water intoxication with serum sodium levels as low as 100 mmol/l.

During withdrawal, AVP levels increase to high levels within a few hours, reaching highest levels in delirium tremens, and return to normal levels within 4–10 days. The high AVP levels are not associated with appreciable changes in plasma osmolality (22), and elevated plasma AVP levels during withdrawal were associated with overhydration. Therefore, administration of parenteral fluid to withdrawing patients should be undertaken with caution. In addition, because alcohol withdrawal may cause substantial disturbances in electrolyte homoeostasis, blood electrolytes should be monitored closely. After alcohol withdrawal, AVP levels decrease, and excretion of water, sodium and chloride increase resulting in normalization of the expanded extracellular fluid volume within several days.

Remarkably, AVP levels are persistently decreased in long-term abstinent alcoholics, and it has been suggested that the suppressed AVP levels may reflect a dysregulation in the brain that influences the function of the HPA axis, mood, memory, addiction behaviour, and craving during alcohol abstinence (23).

The mechanisms by which alcohol interferes with AVP secretion are not entirely understood. Possible mechanisms include genetically determined or alcohol-induced reduced AVP expression in hypothalamic neurons, insufficient secretion of AVP by the posterior pituitary, alcohol-induced resetting of osmoreceptors, and renal hypersensitivity to AVP. In addition, regulation of fluid balance and electrolyte homeostasis is highly complex and particularly in chronic alcoholism influenced by many factors. Additional factors include atrial natriuretic peptide, possible chronic hypervolaemia, alterations in the renin–angiotensin–aldosterone system, increased plasma cortisol levels, liver and/or renal failure, cardiomyopathy, malnutrition, vomiting, diarrhoea, and others.

Hypertension and alcohol

The recent literature has consistently shown a firm association between hypertensive disease and chronic alcohol consumption. The relative risk estimates for alcohol-induced hypertension in females and males are shown in Table 2.6.4.3 (17). Whereas acute alcohol intake causes peripheral vasodilatation with a consequent fall of blood pressure, chronic alcohol consumption increases the blood pressure in a dose-dependent manner. Several studies have established chronic consumption of three standard drinks (8–10 g of alcohol per drink) as the threshold for raising blood pressure. Below this threshold, results have been less consistent. Alcohol increases systolic and—to a somewhat smaller degree—diastolic blood pressure. Most studies show a linear relationship between blood pressure and alcohol intake, although J- and U-shaped curves have also been reported.

The exact mechanisms by which alcohol raises blood pressure are not entirely understood, and it is likely that different mechanisms are effective in different people. Possible mechanisms of alcohol-induced hypertension include impairment of baroreceptor control, increase of sympathetic activity, activation of the renin–angiotensin–aldosterone system, increase in cortisol levels, increased shift of calcium to the intracellular space, increased release of endothelin (potent vasoconstrictors, from endothelium), inhibition of endothelium-dependent nitric oxide production (vasodilator), and chronic subclinical withdrawal (20).

Reduction in alcohol intake is effective in lowering blood pressure in both hypertensives and normotensives and may help to prevent the development of hypertension. Therefore, cessation or at least marked reduction of alcohol consumption is the first step in the treatment of alcohol-induced hypertension. Pharmacological treatment should be considered if blood pressure continues to be elevated 2–4 weeks after cessation of alcohol intake. By contrast, hypotension may develop in alcoholics with alcohol-induced autonomic neuropathy and/or late-stage cardiomyopathy.

Growth hormone and alcohol

Alcohol clearly impairs the spontaneous secretion of growth hormone, although the underlying aetiology remains unresolved. Ethanol administration to healthy human volunteers results in a significant and dose-dependent decrease of the nocturnal growth hormone surge. Studies in alcohol-dependent patients have shown a significantly blunted growth hormone response to challenge (e.g. apomorphine). The blunted growth hormone response appears related to alcohol dependence rather than the severity of alcohol withdrawal symptoms, and is associated with early relapse. The association between early relapse and a lower growth hormone response to challenge was suggested to reflect an altered balance of somatostatin to somatotropin releasing hormone (GHRH) that also affects slow wave sleep (SWS) in alcohol-dependent patients. During SWS δ‎ wave activity, the hypothalamus releases GHRH, which causes the pituitary to release growth hormone. Alcohol-dependent patients have lower levels of SWS power and growth hormone release than normal patients (24).

Insulin-like growth factor 1 (IGF-1) is an important anabolic agent, and an essential component of the endocrine system responsible for maintaining lean body mass. Physiological and pathophysiological fluctuations in IGF-1 can markedly influence whole body and muscle protein balance. In addition, IGF-1 is now recognized as an important immunomodulator. The synthesis and secretion of IGF-1 by the liver can be stimulated by elevations in growth hormone or decreased by an elevation in glucocorticoids. Studies in humans with alcoholic hepatitis and alcoholic cirrhosis have shown marked reductions in IGF-1 concentrations. While nutritional status and liver dysfunction are important contributors to this decrease, a reduction in IGF-1 has also been demonstrated in long-term alcohol users without evidence of significant liver disease or malnutrition (25). Disruption of IGF-1 signalling is implicated in the aetiology of alcoholic myopathy. However, further research is needed to establish the role of the IGF system in human alcohol disease.

Parathyroid hormone and alcohol

Reports on parathyroid hormone show inconsistent results in chronic alcoholism. Transient hypothyroidism has been observed with acute alcohol intoxication, followed by a rebound hyperparathyroidism. Disturbances in electrolyte homoeostasis (calcium, magnesium, phosphorus, and potassium) are frequent findings in alcoholism, and mainly due to poor intake, vomiting, diarrhoea, and increased urinary loss. Severe magnesium depletion can result in reduced secretion of parathyroid hormone and end-organ (in bone and kidney) resistance to parathyroid hormone, and thus cause hypocalcaemia. In this case, magnesium administration alone leads to clinical improvement and normalization of calcium abnormalities (26). Calcium and vitamin D supplementation are not appropriate for the treatment of hypocalcaemia secondary to magnesium deficiency. Furthermore, as magnesium is a predominantly intracellular cation, serum magnesium does not always correlate with total body depletion. Therefore, intraerythrocytic magnesium determination is sometimes needed (26).

Bone disease and alcohol

Chronic and heavy alcohol consumption eventually results in an osteopenic skeleton, and increased risk for osteoporosis. Frequent findings include a low bone mass (osteopenia), decreased bone formation, increased frequency of fractures from falls, and delayed and/or complicated fracture healing. The onset of bone loss precedes the increased risk of fractures by one or two decades, and is asymptomatic during this interval. However, when it is exacerbated by various factors, especially liver disease, symptoms of osteoporosis and osteomalacia often manifest. Additional confounding factors include malnutrition, malabsorption, liver disease, hypogonadism, cigarette smoking, age, gender, and others, although their contributory role is still controversial (27). Rare manifestations of skeletal pathology in alcoholism include aseptic necrosis of the femur head, and bone disease resulting from hypercortisolism in pseudo-Cushing’s syndrome, or secondary hyperparathyroidism in alcohol-induced renal failure.

Alcohol-induced osteopenia is distinct from disuse osteoporosis and postmenopausal osteoporosis, where the rate of bone remodelling is increased. Plasma osteocalcin, a marker of bone formation, is reduced and restored during abstinence, whereas calcium-regulating hormones (parathyroid hormone, calcitonin, and vitamin D metabolites) show inconsistent results (27). By contrast, moderate alcohol consumption may result in increased bone mass, particularly in postmenopausal women. In addition, persons who consume 0.5–1.0 drink per day have a lower risk of hip fracture compared with abstainers and heavier drinkers. However, the available literature is insufficient to determine the precise range of alcohol consumption that would maximize bone density and minimize hip fracture (28).

The mechanisms by which alcohol induces bone disease are not fully understood. Clinical and experimental studies indicate that alcohol directly suppresses osteoblast activity and disturbs cell signalling, thus leading to decreased bone formation, and decreased synthesis of an ossifiable matrix, resulting in deficient healing, while probably only small changes occur in bone resorption. The toxic effects of alcohol on osteoblast activity are dose dependent and some studies show that bone loss is greater with longer duration of alcohol consumption. Despite remaining unsolved issues, therapeutic recommendations clearly must highlight the importance of abstinence from alcohol consumption in affected alcohol-dependent individuals (27).

Diabetes mellitus and alcohol

Intake of light to modest amounts of alcohol (10–30 g/day) is associated with enhanced insulin sensitivity, and may thus contribute to some beneficial effects of alcohol in type 2 diabetes. Therefore, light to modest consumption of alcohol in people with type 1 and type 2 diabetes must not be restricted. Larger doses of alcohol, however, were shown to impair glucose uptake by peripheral tissues (29), but there is little evidence from epidemiological studies (24) that chronic alcohol consumption per se increases the risk to develop diabetes mellitus, in general (Table 2.6.4.3). By contrast, diabetes mellitus is frequently found in patients with alcoholic liver cirrhosis. In animals, chronic alcohol administration also increases secretion of glucagon and other hormones that raise blood glucose levels. In addition, alcohol can induce diabetes mellitus through pancreatic destruction (29). Moreover, in a Japanese study alcoholics with diabetes had a significantly lower survival rate than other alcoholics. Treatment of alcohol-associated diabetes mellitus must emphasize abstinence from alcohol, which—in the absence of severe pancreatic or liver disease—may be curative. When pharmacological treatment includes metformin, patients must be instructed to avoid consuming excessive amounts of alcohol because of the increased risk to develop a potentially life-threatening lactic acidosis.

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