Androgens safety and side effects, availability over the counter, health benefit and risks by Ray Sahelian, M.D.

April 21 2014

The term androgen is used to denote hormones such as DHEA hormone, androstenedione hormone, and testosterone, which is only available by a doctor's prescription. DHEA is sold online or over the counter in health food stores where you can purchase it without a prescription. Makes sure you read the article on this hormone before considering its use. Some argue that DHEA is not a true androgen hormone but I think it is. Taking it increases libido and has testosterone like effects. If you plan to take androgens in order to enhance your libido, consider instead natural Erectile Dysfunction herbs that are effective and much safer. Some of these include tribulus terrestris and tongkat ali.

How they are made
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.

Would you consider 7keto dhea an androgen?
   Probably, but I cannot be certain at this time how much of an androgenic effect 7-Keto-DHEA has.

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.

Excess, safety, side effects, risks
Signs and symptoms of excessive androgen secretion (hyperandrogenism) in adolescent and adult women include hirsutism, severe acne, and irregular menses.

Mymensingh Med J. 2014 Jan. Acne vulgaris related to androgens - a review. Sebum production is stimulated by androgens and is the key in the development of acne vulgaris. Several investigators have looked for direct relationships between serum androgen levels, sebum secretion rate and the presence of acne. The presence of acne in prepubertal girls and sebum production in both sexes correlate with serum dehydroepiandrosterone sulfate (DHEAS) levels. Although increased serum androgen levels correlate with the presence of severe nodular acne in men and women, these levels are often within the normal range in mild to moderate acne. This raises the question of whether there is an increased local production of androgens within the sebaceous gland of patients with acne vulgaris that leads to increased sebum secretion.

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.

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.

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.

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.

Anti 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.

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.

SOCIETY FOR THE STUDY OF ANDROGEN DEFICIENCY
DIAGNOSIS AND TREATMENT
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.

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.

St. John's Wort herb
Effects of St John's wort (Hypericum perforatum) extract on plasma androgen concentrations in healthy men and women: a pilot study.
Phytother Res. 2005.
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) 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 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 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.