Alcohol
and Hormones
article syndicated from NIAAA
Alcohol
and Hormones
Hormones
are chemical messengers that control and coordinate
the functions of all tissues and organs. Each hormone
is secreted from a particular gland and distributed
throughout the body to act on tissues at different
sites. Two areas of the brain, the hypothalamus
and the pituitary, release hormones, as do glands
in other parts of the body, such as the thyroid,
adrenal glands, gonads, pancreas, and parathyroid.
For hormones to function properly, their amount
and the timing of their release must be finely
coordinated, and the target tissues must be able
to respond to them accurately. Alcohol can impair
the functions of the hormone-releasing glands and
of the target tissues, thereby causing serious
medical consequences.
Hormones
control four major areas of body function: production,
utilization, and storage of energy; reproduction;
maintenance of the internal environment (e.g., blood
pressure and bone mass); and growth and development.
This Alcohol Alert describes how, by interfering
with hormone actions, alcohol can alter blood sugar
levels and exacerbate or cause diabetes (1-4); impair
reproductive functions (5,6); and interfere with
calcium metabolism and bone structure, increasing
the risk of osteoporosis (7). Conversely, hormones
also may affect alcohol consumption by influencing
alcohol-seeking behavior.
Alcohol
Impairs Regulation of Blood Sugar Levels
The
sugar glucose is the main energy source for all tissues.
Glucose is derived from three sources: from food; from
synthesis (manufacture) in the body; and from the breakdown
of glycogen, a form of glucose that the body stores
in the liver. Hormones help to maintain a constant
concentration of glucose in the blood. This is especially
important for the brain because it cannot make or store
glucose but depends on glucose supplied by the blood.
Even brief periods of low glucose levels (hypoglycemia)
can cause brain damage.
Two
hormones that are secreted by the pancreas and that
regulate blood glucose levels are insulin and glucagon.
Insulin lowers the glucose concentration in the blood;
glucagon raises it. Because prevention of hypoglycemia
is vital for the body, several hormones from the
adrenal glands and pituitary back up glucagon function.
Alcohol
consumption interferes with all three glucose sources
and with the actions of the regulatory hormones. Chronic
heavy drinkers often have insufficient dietary intake
of glucose (8). Without eating, glycogen stores are
exhausted in a few hours (1). In addition, the body's
glucose production is inhibited while alcohol is being
metabolized (2). The combination of these effects can
cause severe hypoglycemia 6 to 36 hours after a binge-
drinking episode (1).
Even
in well-nourished people, alcohol can disturb blood
sugar levels. Acute alcohol consumption, especially
in combination with sugar, augments insulin secretion
and causes temporary hypoglycemia (9). In addition,
studies in healthy subjects (10) and insulin-dependent
diabetics (3) have shown that acute alcohol consumption
can impair the hormonal response to hypoglycemia.
Chronic heavy drinking,
in contrast, has been associated with excessive blood glucose levels (hyperglycemia).
Chronic alcohol abuse can reduce the body's responsiveness to insulin and cause
glucose intolerance in both healthy individuals (11) and alcoholics with liver
cirrhosis (12). In fact, 45 to 70 percent of patients with alcoholic liver
disease are glucose intolerant or are frankly diabetic (1). In animals, chronic
alcohol administration also increases secretion of glucagon and other hormones
that raise blood g lucose levels (13).
Alcohol
consumption can be especially harmful in people with
a predisposition to hypoglycemia, such as patients
who are being treated for diabetes (3,4). Alcohol can
interfere with the management of diabetes in different
ways. Acute as well as chronic alcohol consumption
can alter the effectiveness of hypoglycemic medications
(14,15). Treatment of diabetes by tight control of
blood glucose levels is difficult in alcoholics, and
both hypoglycemic and hyperglycemic episodes are common
(4). In a Japanese study, alcoholics with diabetes
had a significantly lower survival rate than other
alcoholics (16).
Alcohol
Impairs Reproductive Functions
The
human reproductive system is regulated by many hormones.
The most important are androgens (e.g., testosterone)
and estrogens (e.g., estradiol). They are synthesized
mainly by the testes and the ovaries and affect reproductive
functions in various target tissues. Other reproductive
hormones are synthesized in the hypothalamus and pituitary.
Although men and women produce many of the same hormones,
their relative concentrations and their functions vary.
In
men, reproductive hormones are responsible for sexual
maturation, sperm development and thus fertility, and
various aspects of male sexual behavior. In women,
hormones promote the development of secondary sexual
characteristics, such as breast development and distribution
of body hair; regulate the menstrual cycle; and are
necessary to maintain pregnancy. Chronic heavy drinking
can interfere with all these functions. Its most severe
consequences in both men and women include inadequate
functioning of the testes and ovaries, resulting in
hormonal deficiencies, sexual dysfunction, and infertility
(5,6).
Alcohol
is directly toxic to the testes, causing reduced testosterone
levels in men. In a study of normal healthy men who
received alcohol for 4 weeks, testosterone levels declined
after only 5 days and continued to fall throughout
the study period (17). Prolonged testosterone deficiency
may contribute to a "femininization" of male sexual
characteristics, for example breast enlargement (18).
In
addition, animal studies have shown that acute alcohol
administration affects the release of hormones from
the hypothalamus and pituitary (5). Even without a
detectable reduction of testosterone levels, changes
in these hormones can contribute to the impairment
of male sexual and reproductive functions (19). Alcohol
also may interfere with normal sperm structure and
movement by inhibiting the metabolism of vitamin A
(20), which is essential for sperm development.
In
premenopausal women, chronic heavy drinking can contribute
to a multitude of reproductive disorders. These include
cessation of menstruation, irregular menstrual cycles,
menstrual cycles without ovulation, early menopause,
and increased risk of spontaneous abortions (6,21,22).
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 abuse, such as liver disease, pancreatic
disease, malnutrition, or fetal abnormalities (6).
Although
most of these reproductive problems were found in alcoholic
women, some also were observed in women classified
as social drinkers, who drank about three drinks per
day during a 3-week study (23). A significant number
of these women had abnormal menstrual cycles and a
delay or lack of ovulation.
Alcohol
also affects reproductive hormones in postmenopausal
women. After menopause, estradiol levels decline drastically
because the hormone is no longer synthesized in the
ovaries, and only small amounts are derived from the
conversion of testosterone in other tissues. This estradiol
deficiency has been associated with an increased risk
for cardiovascular disease and osteoporosis in po stmenopausal
women (24). Alcohol can increase the conversion of
testosterone into estradiol (25). Accordingly, postmenopausal
women who drank (24,26) were found to have higher estradiol
levels than abstaining women. Studies have shown that
in postmenopausal women, three to six drinks per week
may reduce the risk of cardiovascular disease (27)
without significantly impairing bone quality (24) or
increasing the risk of alcoholic liver disease (28)
or breast cancer (29).
Alcohol
Impairs Calcium Metabolism and Bone Structure
Calcium
exists in two forms in the body. The main reservoirs
are the bones and teeth, where the calcium content
determines the strength and the stiffness of the bones.
The rest of the body's calcium is dissolved in the
body fluids. Calcium is important for many body functions,
including communication between and within cells. The
overall calcium levels depend on how much calcium is
in the diet, how much is absorbed into the body, and
how much is excreted. Calcium absorption, excretion,
and distribution between bones and body fluids are
regulated by several hormones, namely parathyroid hormone
(PTH); vitamin D-derived hormones; and calcitonin,
which is made by specific cells in the thyroid.
Alcohol
can interfere with calcium and bone metabolism in
several ways. Acute alcohol consumption can lead
to a transient PTH deficiency and increased urinary
calcium excretion, resulting in loss of calcium from
the body (30). Chronic heavy drinking can disturb
vitamin D metabolism, resulting in inadequate absorption
of dietary calcium (31).
Studies
in alcoholics also have shown that alcohol is directly
toxic to bone-forming cells and inhibits their activity
(32-34). In addition, chronic heavy drinking can adversely
affect bone metabolism indirectly, for example by contributing
to nutritional deficiencies of calcium or vitamin D
(7). Liver disease and altered levels of reproductive
hormones, both of which can be caused by alcohol, also
affect bone metabolism (7).
Calcium
deficiency can lead to bone diseases, such as osteoporosis.
Osteoporosis is characterized by a substantial loss
of bone mass and, consequently, increased risk of fractures.
It affects 4 million to 6 million mainly older Americans,
especially women after menopause. In alcoholics, the
risk of osteoporosis is increased (35). Because many
falls are related to alcohol use (36), adverse alcohol
effects on bone metabolism pose a serious health problem.
Studies
with abstinent alcoholics have found that alcohol-induced
changes in bone metabolism, including toxic effects
on bone-forming cells, are at least partially reversible
after cessation of drinking (32,33,37,38).
Hormones
May Influence Alcohol-Seeking Behavior
The
effects of alcohol on different hormonal pathways may
in turn influence alcohol-seeking behavior. For example,
in animals, alcohol-seeking behavior appears to be
regulated in part through a system called the renin-angiotensin
system, which controls blood pressure and salt concentrations
in the blood. In rats, activation of this system through
alcohol consumption caused the animals to reduce their
alcohol intake (39). The mechanism and relevance of
this effect are currently under investigation.
Alcohol
and Hormones--A Commentary by
NIAAA Director Enoch Gordis, M.D.
Alcohol's wide-ranging
effects on the hormone system present many practical clinical concerns. For
example, managing diabetes, particularly with the current emphasis on stringent
control of blood sugar, is complicated by alcohol's interference with blood
sugar levels. In the emergency room, stupor in patients with alcohol on their
breath often is not caused by alcohol intoxication, but by the hypoglycemia
(low blood sugar) that is a complication of heavy drinking. Failure to treat
the hypoglycemia could have life-threatening consequences. Heavy drinking has
a major effect on the reproductive system, affecting libido, fertility, and
pregnancy. Heavy drinking also places postmenopausal women at risk for fractures
from falls due to their increased risk for osteoporosis from alcohol's effect
on blood estrogen levels coupled with their increased risk of falling due to
drinking. However, it is possible that moderate alcohol use may help protect
postmenopausal women against osteoporosis by raising blood estrogen levels.
Scientists are working to discover for which population this may be true and
at what drinking levels. Finally, research on how alcohol's interactions with
hormones may contribute to the pathological drive to consume alcohol is just
beginning and may provide valuable insight into the mechanisms by which alcohol-seeking
behavior can be controlled.
References
(1)
Gordon, G.G., & Lieber, C.S. Alcohol,
hormones, and metabolism. In: Lieber, C.S.,
ed. Medical and Nutritional Complications
of Alcoholism. New York: Plenum Publishing
Corp., 1992. pp. 55-90. (2) Sneyd, J.G.T. Interactions
of ethanol and carbohydrate metabolism.
In: Crow, K.E., and Batt, R.D., eds. Human
Metabolism of Alcohol, Vol. 3. Boca
Raton, FL: CRC Press, 1989. pp. 115-124.
(3) Avogaro, A.; Beltramello, P.; Gnudi,
L.; Maran, A.; Valerio, A.; Miola, M.;
Marin, N.; Crepladi, C.; Confortin, L.;
Costa, F.; MacDonald, I.; & Tiengo,
A. Alcohol intake impairs glucose counterregulation
during acute insulin-induced hypoglycemia
in IDDM patients: Evidence for a critical
role of free fatty acids. Diabetes 42(11):1626-1634,
1993. (4) Crane, M., & Sereny,
G. Alcohol and diabetes. British Journal
of Addiction 83(12):1357-1358, 1988. (5)
Emanuele, M.A.; Halloran, M.M.; Uddin,
S.; Tentler, J.J.; Emanuele, N.V.; Lawrence,
A.M.; & Kelley, M.R. The effects of
alcohol on the neuroendocrine control of
reproduction. In: Zakhari, S., ed. Alcohol
and the Endocrine System. National
Institute on Alcohol Abuse and Alcoholism
Research Monograph No. 23. NIH Pub. No.
93-3533. Bethesda, MD: National Institutes
of Health, 1993. pp. 89-116. (6) Mello,
N.K.; Mendelson, J.H.; & Teoh,
S.K. An overview of the effects of alcohol
on neuroendocrine function in women. In:
Zakhari, S., ed. Alcohol and the Endocrine
System. National Institute on Alcohol
Abuse and Alcoholism Research Monograph
No. 23. NIH Pub. No 93-3533. Bethesda,
MD: National Institutes of Health, 1993.
pp. 139-170. (7) Laitinen, K., & Valimaki,
M. Bone and the "comforts of life." Annals
of Medicine 25(4):413-425, 1993. (8)
Palmer, T.N.; Cook, E.B.; & Drake,
P.G. Alcohol abuse and fuel homeostasis.
In: Palmer, T.N., ed. Alcoholism: A
Molecular Perspective. NATO ASI Series.
Series A, Life Sciences Vol. 206. New York:
Plenum Press, 1991. pp. 223-235. (9)
O'Keefe, S.J., & Marks, V. Lunchtime
gin and tonic a cause of reactive hypoglycemia. Lancet 1(8025):1286-1288,
1977. (10) Kolaczynski, J.W.; Ylikahri,
R.; Harkonen, M.; & Koivisto, V.A.
Acute effect of ethanol on counterregulatory
response and recovery from insulin-induced
hypoglycemia. Journal of Clinical Endocrinology
and Metabolism 67(2):384-388, 1988. (11)
Shah, J.H. Alcohol decreases insulin
sensitivity in healthy subjects. Alcohol
and Alcoholism 23(2):103-109, 1988. (12)
Letiexhe, M.R.; Scheen, A.J.; Gerard,
P.L.; Bastens, B.H.; Pirotte, J.; Belaiche,
J.; & Lefebvre, P.J. Insulin secretion,
clearance, and action on glucose metabolism
in cirrhotic patients. Journal of Clinical
Endocrinology and Metabolism 77(5):1263-1268,
1993. (13) Adams, M.A., & Hirst,
M. Adrenal and urinary catecholamines during
and after severe ethanol intoxication in
rats: A profile of changes. Pharmacology,
Biochemistry and Behavior 21(1):125-131,
1984. (14) Lewis, H., & Kendall,
M.J. Alcohol and treatment of diabetes. Journal
of Clinical Pharmacy and Therapeutics 13:312-328,
1988. (15) Angelini, P.; Vendemiale,
G.; & Altomare, E. Alcohol and diabetes
mellitus. Alcologia 4(2):109-111,
1992. (16) Yokoyama, A.; Matsushita,
S.; Ishii, H.; Takagi, T.; Maruyama, K.; & Tsuchiya,
M. Impact of diabetes mellitus on the prognosis
of alcoholics. Alcohol and Alcoholism 29(2)181-186,
1994. (17) Gordon, G.C.; Altman,
K.; Southren, A.L.; Rubin, E.; & Lieber,
C.S. The effects of alcohol (ethanol) administration
on sex hormone metabolism in normal men. New
England Journal of Medicine 295:793-797,
1976. (18) Bannister, P., & Lowosky,
M.S. Ethanol and hypogonadism. Alcohol
and Alcoholism 22(3):213-217, 1987. (19)
Bartke, A. Chronic disturbances of
the hypothalamic-pituitary-testicular axis:
Effects on sexual behavior and fertility.
In: Zakhari, S., ed. Alcohol and the
Endocrine System. National Institute
on Alcohol Abuse and Alcoholism Research
Monograph No. 23. NIH Pub. No. 93-3533.
Bethesda, MD: National Institutes of Health,
1993, pp. 69-87. (20) Leo, M.A., & Lieber,
C.S. Hepatic vitamin A depletion in alcoholic
liver injury. New England Journal of
Medicine 307(10):597-601, 1982. (21)
Alcohol and abortion. New Zealand
Medical Journal 92:353, 1980. (22)
Kline, J.; Levin, B.; Stein, Z.; Susser,
M.; & Warburton, D. Epidemiologic detection
of low dose effects on the developing fetus. Environmental
Health Perspectives 42:119-126, 1981. (23)
Mendelson, J.H., & Mello, N.K.
Chronic alcohol effects on anterior pituitary
and ovarian hormones in healthy women. Journal
of Pharmacological and Experimental Therapy 245:407-412,
1988. (24) Gavaler, J.S., & Van
Thiel, D.H. The association between moderate
alcoholic beverage consumption and serum
estradiol and testosterone levels in normal
postmenopausal women: Relationship to the
literature. Alcoholism: Clinical and
Experimental Research 16(1):87-92,
1992. (25) Gordon, G.G.; Southren,
A.L.; Vittek, J.; & Lieber, C.S. Effect
of alcohol ingestion on hepatic aromatase
activity and plasma steroid hormones in
the rat. Metabolism 28(1):20-24,
1979. (26) Gavaler, J.S., & Van
Thiel, D.H. Hormonal status of postmenopausal
women with alcohol-induced cirrhosis: Further
findings and a review of the literature. Hepatology 16(2):312-319,
1992. (27) Stampfer, M.J.; Colditz,
G.A.; Willett, W.C.; Speizer, F.E.; & Hennekens,
C.H. A prospective study of moderate alcohol
consumption and the risk of coronary disease
and stroke in women. New England Journal
of Medicine 319:267-273, 1988. (28)
Gavaler, J.S.; Kelly, R.H.; Wight,
C.; Sanghvi, A.; Cauley, J.; Belle, S.; & Brandt,
K. Does moderate alcoholic beverage consumption
affect liver function/injury tests in postmenopausal
women? Alcoholism: Clinical and Experimental
Research 12(2):337, 1988. (29) Willett,
W.C.; Stampfer, M.J.; Colditz, G.A.;
Rosner, B.A.; Hennekens, C.H.; & Speizer,
F.E. Moderate alcohol consumption and the
risk of breast cancer. New England Journal
of Medicine 316:1174-1180, 1987. (30)
Laitinen, K.; Lamberg-Allardt, C.;
Tunninen, R.; Karonen, S.L.; Tahetla, R.;
Ylikahri, R.; & Valimaki, M. Transient
hypoparathyroidism during acute alcohol
intoxication. New England Journal of
Medicine 324(11):721-727, 1991. (31)
Bjorneboe, A.-E.A.; Bjorneboe, A.;
Johnsen, J.; Skylv, N.; Oftebro, H.; Gautvik,K.M.;
Hoiseth, A.; Morland, J.; & Drevon,
C.A. Calcium status and calcium-regulating
hormones in alcoholics. Alcoholism:
Clinical and Experimental Research 12(2):229-232,
1988. (32) Jaouhari, J.; Schiele,
F.; Pirollet, P.; Lecomte, E.; Paille,
F.; & Artur, Y. Concentration and hydroxyapatite
binding capacity of plasma osteocalcin
in chronic alcoholic men: Effect of a three-week
withdrawal therapy. Bone and Mineral 21(3):171-178,
1993. (33) Pepersack, T.; Fuss,
M.; Otero, J.; Bergmann, P.; Valsamis,
J.; & Corvilain, J. Longitudinal study
of bone metabolism after ethanol withdrawal
in alcoholic patients. Journal of Bone
and Mineral Research 7(4):383-387,
1992. (34) Bikle, D.D.; Stesin,
A.; Halloran, B.; Steibach, L.; & Recker,
R. Alcohol-induced bone disease: Relationship
to age and parathyroid hormone levels. Alcoholism:
Clinical and Experimental Research 17(3)690-695,
1993. (35) Rico, H. Alcohol and
bone disease. Alcohol and Alcoholism 25(4):345-352,
1990. (36) Hingson, R., & Howland,
J. Alcohol as a risk factor for injury
or death resulting from accidental falls:
A review of the literature. Journal
of Studies on Alcohol 48(3):212-219,
1987. (37) Gonzalez-Calvin, J.L.; Garcia-Sanchez,
A.; Bellot, V.; Munoz-Torres, M.; Raya-Alvarez,
E.; & Salvatierra-Rios, D. Mineral
metabolism, osteoblastic function and bone
mass in chronic alcoholism. Alcohol
and Alcoholism 28(5):571-579, 1993. (38)
Laitinen, K.; Lamberg-Allardt, C.;
Tunninen, R.; Harkonen, M.; & Valimaki,
M. Bone mineral density and abstention-induced
changes in bone and mineral metabolism
in noncirrhotic male alcoholics. American
Journal of Medicine 93(6):642-650,
1992. (39) Grupp, L.A. The renin-angiotensin
system as a regulator of alcohol consumption:
A review and some new insights. In: Zakhari,
S., ed. Alcohol and the Endocrine System. National
Institute on Alcohol Abuse and Alcoholism
Research Monograph No. 23. NIH Pub. No.
93-3533. Bethesda, MD: National Institutes
of Health, 1993. pp. 37-65.
ACKNOWLEDGMENT: The National Institute
on Alcohol Abuse and Alcoholism wishes to acknowledge
the valuable contributions of Judith Fradkin, M.D., Chief,
Endocrinology and Metabolic Diseases Program Branch,
National Institute of Diabetes and Digestive and Kidney
Diseases, to the development of this Alcohol Alert.
article
syndicated from National
Institute on Alcohol Abuse and Alcoholism:
http://www.niaaa.nih.gov/publications/aa26.htm
National Institute on Alcohol Abuse and Alcoholism No. 26 PH 352, October 1994