National Institute on Alcohol Abuse and Alcoholism No. 26 PH 352 October 1994
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, Suite 409, 6000 Executive Boulevard, MSC 7003, Bethesda, MD
20892-7003. Telephone: 301-443-3860
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