The term androgen is used to denote hormones such as DHEA, androstenedione, and testosterone. Some argue that DHEA is not a true androgen hormone.
The Making of Androgens
Androgens and estrogens are primarily made from dehydroepiandrosterone (DHEA),
which is made from cholesterol by four enzymatic steps. First, cholesterol
enters the mitochondria. Second, within the mitochondria, cholesterol is
converted to pregnenolone. Third, pregnenolone undergoes 17alpha-hydroxylation.
Finally, 17-OH pregnenolone is converted to DHEA.
Androgen deficiency
A decrease in androgen levels with age occurs at about the rate of
a 1 percent drop in testosterone each year after the age of 30.
Age-related changes in male body composition are mainly related to the
progressive decrease in the level of circulating anabolic hormones, among
which testosterone (T) is rather important. Its decline, between the ages
of 35 and 75, is associated to a loss of muscle mass and fibers number, a
doubling of fat mass and a decrease in bone mineral density by 0.3% per yr
after age 35. In addition to changes in muscle mass and bone tissue,
androgen deficiency can lead to a decrease in cognition, loss of
sexual desire,
and lack of vitality.
Androgen excess
Signs and symptoms of excessive
androgen secretion (hyperandrogenism) in adolescent and adult women
include hirsutism, severe
acne, and irregular menses.
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Androgens
and Weight Loss
A condition involving abnormally high levels of androgens (steroid
hormones) known in medical circles as "hyperandrogenemia" starts early in obese
children, possibly placing them at increased risk for the metabolic syndrome --
a cluster of conditions such as high blood pressure and high blood sugar levels
that raise the risk of heart disease and diabetes. Weight loss leads to
decreasing androgen levels. Androgens are steroid hormones such as testosterone
or androsterone, which control the development and maintenance of masculine
characteristics in both males and females.
Androgens and Women
Androgens in women either derive from direct ovarian production or from
the peripheral conversion of the adrenal sex steroid precursor
dehydroepiandrosterone - dhea - to the active androgens. Therefore, loss of
adrenal or ovarian function, as in Addison's disease or after bilateral
oophorectomy, usually results in severe androgen deficiency. Androgen
replacement in these women may produce significant improvements, particularly in
libido and mood. Physiological menopause is not necessarily associated with
androgen deficiency and therefore does not routinely require androgen therapy.
The number of randomized controlled trials of androgen use in women is still
limited. Choosing both a convenient and efficient mode of androgen
administration in women remains a challenge and currently none of the available
preparations is officially approved for use in women.
Menopause doesn't mean total ovarian failure. The
function of stromal cells is maintained and steroids, especially androgens, are
produced. The role of androgenesis after menopause is important because of
general androgens activity and their influence on some symptoms characteristic
for perimenopausal period. Androgens are necessary for the proper quality of
life connected with bone mass density, libido, mood and physical activity.
Knowledge of postmenopausal ovarian androgenesis and its influence on total
androgens level is still not complete.
Androgens and Teenage Girls
Girls who are obese during the early stages of puberty have an increased
risk of developing abnormally high levels of androgens. This condition, referred
to as hyperandrogenemia, is characterized by high levels of androgens, such as
testosterone or androsterone, hormones that control the development masculine
characteristics. Hyperandrogenemia is also associated with the later development
of polycystic ovarian syndrome, a condition that includes infertility, obesity,
abnormal menstrual cycles, and excessive hair growth.
Androgens and Bone
Metabolism
Bone health and strength are dependent on the coupling of bone
resorption and bone formation. This process is governed by the interaction
of osteoclasts and osteoblasts. Both sex steroids-
estrogen (E) and
testosterone (T)- have receptors on all bone cells, with androgen
dominance on osteoblasts and osteocytes. Specific receptors for the weaker
androgens, such as DHEA have also been identified. Androgens increase bone mass in specific skeletal
compartments through effects on bone cells, enhancing osteoblast activity but
inhibiting that of osteoclasts.
Testosterone acts both directly and via its
aromatization to estradiol. The activity of the androgens also varies with
the bone surface; periosteal cells, for example, do not have
5alpha-reductase activity, indicating that testosterone is the active
metabolite at this clinically important site. Androgens influence bone
cell function via local and systemic growth factors and
cytokines. By
enhancing osteoblast differentiation, androgens regulate bone matrix
production, organization, and mineralization. Androgens also regulate
osteoclast recruitment and activity. Endogenous androgens increase bone
mineral density (BMD) in both adolescent and adult premenopausal women.
Women with excess endogenous androgen-for example, those with hirsutism and
polycystic ovary syndrome (PCOS)-have increased bone mineral density
compared with normal young women. Estrogen and androgen therapy increases
BMD to a greater degree than does estrogen therapy alone.
Androgen Deprivation therapy for
prostate cancer
Bone mineral density
decreases during androgen deprivation therapy in men with prostate cancer.
A sharp decline in hemoglobin levels after initiating androgen deprivation
therapy to treat advanced prostate cancer is associated with shortened
survival.
Androgen insensitivity syndrome
insensitivity syndrome is a hereditary disease associated with
chromosome X. The occurrence of mild forms of androgenic insensitivity in
the population is not known, but it probably represents large group of
patients with azoospermia (low level of sperm). Androgenic insensitivity
is a common cause of primary amenorrhea.
Anti androgen - androgen
blockade
Androgen deprivation therapy has clear roles in the management of
advanced prostate cancer and high-risk localized disease.
Androgen ablation may be more effective if used early in the clinical
course for patients with nonmetastatic prostate cancer.
Side effects are common with anti androgen therapy.
These include hot flashes; gynecomastia; changes in body composition,
metabolism, and the cardiovascular system; osteoporosis; anemia;
psychiatric and cognitive problems; and fatigue and diminished quality of
life.
Androgen receptor
Androgens directly regulate gene expression via the androgen
receptor, a member of the nuclear receptor superfamily. Nuclear receptors
share a modular structure, with specialized domains for DNA binding,
ligand binding, and transcriptional activation.
Androgen Organization
SOCIETY FOR THE STUDY OF ANDROGEN DEFICIENCY
DIAGNOSIS AND TREATMENT OF ANDROGEN DEFICIENCY
Saturday, June 24th & Sunday, June 25th, 2006
Central London Venue to be announced www.andropause.org.uk
Definitions and descriptions; androgen synthesis, metabolism and action;
testosterone, diabetes, and metabolic syndrome; androgens and circulatory
disorders; Alzheimer's disease, sex steroids and the brain; causes of
androgen deficiency; the androgen receptor and genetic modifications;
clinical and laboratory diagnosis of androgen deficiency; validity of
androgen assays and laboratory tests; the concept of androgen resistance;
androgens and depression, mid-life crisis, trauma and memory loss;
androgens and frailty in the elderly; treatment of androgen deficiency;
safety and prostate cancer; androgens and erectile dysfunction; androgen
deficiency in women; health and safety issues in hypogonadism.
High Androgens and Skin
Manifestations
Hyperandrogenism in women can be caused by various conditions, the
most prevalent of which is polycystic ovary syndrome. Common skin
manifestations of hyperandrogenism include hirsutism, acne, acanthosis
nigricans, and androgenic alopecia. Hirsute women often have increased
activity of
5alpha-reductase, the enzyme that converts the androgen testosterone
to its active metabolite, in hair follicles. Likewise, androgens affect
the formation of acne by increasing sebum production from sebaceous glands
in the skin. The diagnosis of polycystic ovary syndrome includes a
complete history, physical examination with emphasis on evidence of
androgen excess, and appropriate laboratory investigation to exclude other
causes of hyperandrogenism. Treatments for the dermatologic conditions of
hyperandrogenism include lifestyle modification, oral contraceptives,
antiandrogens, and insulin-sensitizing medications.
Androgen and St. John's
Wort
Effects of St John's wort (Hypericum perforatum L.) extract on
plasma androgen concentrations in healthy men and women: a pilot study.
Phytother Res. 2005 Oct;19(10):901-6.
Laboratory of Drug Disposition and Pharmacogenetics, Department of
Psychiatry and Behavioral Sciences, Medical University of South Carolina,
North Charleston, SC
St John's wort extract (SJW; Hypericum perforatum L.) is taken
extensively as a putative herbal antidepressant. It has been shown to
induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the
clearance of numerous drugs and steroids such as cortisol and ethinyl
estradiol. This study was conducted to determine if SJW exposure also
alters the concentrations of circulating androgenic steroid hormones. The
study was conducted using healthy volunteers (6M, 6F) studied before and
after a 14-day treatment period with a SJW preparation previously
demonstrated to induce the activity of CYP3A4. Plasma concentrations of
testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS),
sex hormone-binding globulin (SHBG) and the combined concentrations of
androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were
measured by immunoassay methods. It is concluded that despite significant
induction of CYP3A4, short term administration of SJW does not
significantly alter the concentrations of most circulating androgens in
men and women but may produce a dimunition in some of the circulating
5alpha-reduced androgens.
Androgens questions
Q. Would you consider
7keto dhea an androgen?
A. Probably, but I cannot be certain at this time how much of an
androgenic effect
7-Keto-DHEA has.