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.
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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.
All material contained
in the Alcohol Alert is in the public domain and may be used
or reproduced without permission from NIAAA. Citation of the
source is appreciated.
Copies of the Alcohol
Alert are available free of charge from the Scientific Communications
Branch, Office of Scientific Affairs, NIAAA, Willco Building,
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