Glossary of Male Endocrinology

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Anabolic androgenic steroids (AAS) – This is a group of synthetic hormones related to testosterone which promote muscle growth, strength, and male characteristics. In 1990 AAS’s were classified as Class III controlled substances, becoming illegal to use in the US without a prescription. In 2004, androstenedione and androstenediol related hormones where added to the list of AAS’s. They are now classified as controlled substances. DHEA and Pregnenolone are the only hormones that can be used without a prescription.

Aldosterone – Known as the most powerful mineralocorticoid (hormone involved in sodium retention). Aldosterone stimulates the kidneys to retain more sodium and release potassium, this increases water retention and blood pressure. (10)

Androgen – Any hormone which binds to the androgen receptor and promotes male characteristics such as; muscle, body hair, deep voice, and sexual differentiation. Testosterone, androstenedione, androstenediol, androsterone, are examples of androgens.

Androstanediol – A 5-alpha reduced androgen with an important role in prostate health. It accomplishes this by reducing local aromatase activity. (58) Androstanediol is considered a cutaneous steroid for its ability to stimulate body hair growth. Androstanediol also functions as a neurosteroid positively influencing the feeling of pleasure. (59)

Androstanedione – A 5-alpha reduced androgen with an important role in prostate health. It accomplishes this by reducing local aromatase activity. (58) Androstanedione is considered a cutaneous steroid for its ability to stimulate body hair growth.

4-Androstenediol – A powerful androgen that serves as an immediate precursor to testosterone.

5-Androstenediol – An androgen with minor estrogenic properties. Androstenediol positively influences muscle growth while improving immune system response. (38-41) These positive effects can partly be attributed to androstenediols ability to reduce and ameliorate the effects of cortisol. (42)

4-Androstenedione – A powerful androgen with moderate immunogenic properties. (46,47) Androstenedione has been shown to increase strength and muscle mass, inhibit fat cell division, increase libido, and promote aggressive behavior. (48) Androstenedione readily converts to estrone by interacting with the aromatize enzyme, therefore use of an aromatase inhibitor is necessary to avoid estrogenic side effects from androstenedione.

5-Androstenedione – An intermediate in androstenedione production, with similar androgenic/anabolic properties.

Androstenetriol – An androgen with even more powerful immunogenic properties than its precursor androstenediol. Animal studies show androstenetriol can neutralize the negative effects of glucocorticoids, enhance immune system activity, speed wound healing, and improve the survival rate after traumatic injury. (41,43-45)

Androsterone – A metabolite of the 5-alpha reduced steroids, responsible for supporting sexual function and general male characteristics. (57)

Anti-catabolic – The property of preserving muscle or preventing the breakdown of muscle from cortisol. For instance, testosterone is anabolic, and antagonizes the catabolic effects of cortisol. Therefore, testosterone is anti-catabolic.

Aromatase – Also known as CYP 19. Aromatase is an enzyme mainly produced in the liver, which circulates the blood stream converting testosterone to estrogen. Inhibiting aromatase can lower estrogen production.

3-beta hydroxysteroid dehydrogenase (3b HSD) – The enzyme responsible for several steroid hormone conversions; e.g., androstenediol to testosterone, and DHEA to androstenedione.

Cholesterol - The building block for all steroid hormones. The conversion of cholesterol to pregnenolone is initiated by the transport of cholesterol from the outer to inner mitochondrial membrane, which is known as the rate limiting step in cholesterol mobilization to steroid hormones. This process is regulated by steroid acute regulatory protein (StAR). DHEA has been shown to stimulate StAR protein in human cells, thus enhancing production of steroid hormones. (1)

Cognitive function – The mental processing of information and general act of thinking.

Corticosterone – A weak glucocorticoid and mineralocorticoid released during times of stress. It serves as the main precursor to aldosterone. Corticosterone has been implicated as the hormone responsible for the stress induced reduction of male sexual behavior. (9)

Cortisol – Classified as a glucocorticoid because of effects on glucose metabolism. Also known as a catabolic hormone for its ability to breakdown muscle tissue by converting amino-acids to glucose. (21) Besides being catabolic to muscle tissue, elevated cortisol can suppress androgen and growth hormone production though HPTA inhibition, (21,22) decrease insulin sensitivity, (23) increase fat tissue, (24) suppress the immune system, and cause mental depression. (25) While cortisol’s effects seem negative, it plays a critical role in the repair and regeneration process of bodily tissue, therefore total cortisol elimination is undesired. Rather, its catabolic effects are better neutralized by the anabolic effects of androgens. DHEA and its androgen metabolites have been shown to antagonize these negative effects cortisol. (26-29) Note: The same negative effects seen with cortisol are seen with the use of its synthetic derivatives such as hydrocortisone and prednisone; often prescribed for inflammation diseases. (30)

CYP 11A – The enzyme responsible for converting cholesterol to pregnenolone. This is considered one of the first steps in testosterone synthesis.

11-Deoxycorticosterone – Known as a mineralocorticoid because of its effects on electrolyte balance. 11-Deoxycorticosterone is similar to its metabolite aldosterone in having an effect on blood pressure, water retention and body weight. (8)

11-Deoxycortisol – Classified as a glucocorticoid because of effects on glucose metabolism. 11-Deoxycortisol is similar to cortisol in its ability to synthesize glucose by breaking down amino-acids (muscle tissue). Deoxycortisol is generally considered a catabolic hormone. (20)

DHEA – Dehydroepiandrosterone serves as a main precursor to male androgens. DHEA also serves directly as an anabolic by encouraging growth hormone and IGF-1 synthesis. (12,13) DHEA also plays an important role as a neurosteroid responsible for sexual function, (14,15) feelings of well being, (16) stress management, (17) and improvement of sleep quality. (18,19) However, many of DHEA’s positive effects on muscle growth, fat loss and immune function are a result of its downstream metabolites noted in the following conversions.

7-alpha DHEA – Has thermogenic and immunogenic properties but mainly serves as the intermediate to its more potent down-steam metabolites. (31,32)

7-beta DHEA – The most powerful thermogenic of the DHEA metabolites. (31)

7-keto DHEA – Also known as 7-oxo DHEA and shown to have powerful immune stimulating and thermogenic effects by directly activating the mitochondrial and cytosolic thermogenic enzymes in liver. (32-36) 7-keto DHEA supplementation has also been positively correlated with increased thyroid function. (37)

DHT – Dihydrotestosterone is a 5-alpha reduced androgen with important functions in the reproductive organs. DHT supports sexual arousal and erectile function.(57) DHT also competes with estrogen for the estrogen receptor and helps minimize estrogenic fat depositing and breast tissue growth (gyno).(60)

Estradiol – Otherwise known as E2, estradiol has important functions in muscle growth, bone health, libido, and cholesterol levels. (61-63) However, excessive estradiol can lead to fat storage, loss of libido, gynomastia (bitch tits), cancer proliferation, and negative feedback on the hypothalamus thus limiting androgen production. (64,65) Sustain Alpha has ingredients proven to bind to aromatase (CYP19) and minimize estrogen production. (75-78)

Estriol – Otherwise known as E3 and considered more cancer proliferative than E1 or E2. Estriol has important functions in muscle growth, bone health, libido, and cholesterol levels. (61,62,63) However, excess estriol can lead to fat storage, loss of libido, gynomastia (bitch tits), cancer proliferation, and negative feedback on the hypothalamus thus limiting androgen production. (64,65)

Estrone – Otherwise known as E1 and a weaker estrogen than E2 or E3. Estrone has important functions in muscle growth, bone health, libido, and cholesterol levels.(61,62,63) However, excess estrone can lead to fat storage, loss of libido, gynomastia (bitch tits), cancer proliferation, and negative feedback on the hypothalamus thus limiting androgen production. (64,65) Sustain Alpha  has ingredients proven to bind to aromatase (CYP19) and minimize estrogen production. (75,76,77,78)

Estrogen – A term used to describe all estrogen related hormones, including estradiol, estrone, and estriol. A normal and healthy ratio of estrogens plays an important role in muscle growth, bone health, libido, and cholesterol levels. (61,62,63)

Follicle Stimulating Hormone (FSH) – A hormone sent from the brain (pituitary gland) which stimulates the sertoli cells within the testes to produce sperm. Luteinizing hormone and follicle stimulating hormone act synergistically to support testosterone production and fertility.

Gonadotropin Releasing Hormone (GnRH) – A hormone sent from the hypothalamus to the pituitary gland which stimulates release of luteinizing and follicle stimulating hormone.

Growth Hormone (GH) – In puberty, growth hormone is mainly responsible for bone and cartilage growth. In grown men, growth hormone helps to reduce body fat and increase the creation of new muscle cells, while also increasing calcium retention in bones. GH is released from the pituitary gland by stimulation from growth hormone releasing hormone (GHRH) from the hypothalamus. Growth hormone release can be stimulated by sleep, exercise, and protein. DHEA supplementation has also been shown to increase growth hormone release.(12,13) Growth hormone release is decreased by carbohydrates and cortisol.

Hormone imbalance – This is a term used for having any given hormone too high or too low. For instance, having high cortisol and low androgens would be called cortisol dominance. Having high estrogens and low androgens would be called estrogen dominance. In some cases, men may have too low of estrogen, which would be described as androgen dominance.

Hormone profile – A term used to describe the ratio of all hormones. For instance, a desirable male hormone profile would be described as having high androgens, low estrogens and moderate cortisol. A desirable estrogen profile would be described as having higher 2-hydroxylated estrogens than 4-hydroxylated estrogens.

2-hydroxyestradiol – This is the least cancer proliferative estradiol metabolite, while also being the most readily excreted, therefore 2-hydroxyestradiol is considered a favorable estrogen in cancer prevention.(66,67) 7,8 Benzoflavone has been shown to induce 2-hydroxylation of estrogens.(68)

4-hydroxyestradiol – The 4-hydroxy metabolite of estradiol is known to be a potent carcinogen and inducer of DNA damage.(68,69,70) 4-hydroxyestradiol is also easily converted to toxic quinones in the liver if sufficient anti-oxidants are not available.(71) Animal studies have shown that 7,8 benzoflavone can inhibit the 4-hydroxylation of estrogens and reduce toxic quinine production.(72,73,74)

2-hydroxyestrone – This is the least cancer proliferative estrone metabolite, while also being the most readily excreted, therefore 2-hydroxyestradiol is considered a favorable estrogen in cancer prevention.(66,67) 7,8 Benzoflavone has been shown to induce 2-hydroxylation of estrogens.(68)

4-hydroxyestrone – The 4-hydroxy metabolite of estrone is known to be a potent carcinogen and inducer of DNA damage.(68,69,70) 4-hydroxyestrone is also easily converted to toxic quinones in the liver if sufficient anti-oxidants are not available.(71) Animal studies have shown that 7,8 benzoflavone can inhibit the 4-hydroxylation of estrogens and reduce toxic quinine production.(72,73,74)

16a-hydroxyestrone – The 16a-hydroxylated metabolite is a potent carcinogen of estrone. An increased ratio of 16a-hydroxy estrogens to 2-hydroxy estrogens implicates a high cancer risk.(70)

17a-Hydroxypregnenolone – Major precursor to DHEA. Important in testicular function and also as a neurosteroid.(79)

17a-Hydroxyprogesterone – Serves as a main precursor to both corticosteroids and androgens. Known to have similar properties to progesterone.(20)

17a-hydroxylase (CYP 17) – This enzyme is responsible for the conversion of pregnenolone and progesterone to more active androgens such as DHEA and Androstenedione. 17a-hydroxylase is an important enzyme in testosterone production.

4-hydroxylation – 4-hydroxylation is the interaction between estrogen and CYP 1A2 (or related enzyme) in which the estrogen is turned into a 4-hydroylated metabolite. Eg. Estradiol is 4-hydroxylated to form 4-hydroxyestradiol. 4-hydroxylated metabolites of estrogen are known to cause cancer. (68,69,70,71)

Hypothalamus – A region in the center of the brain that sends signals to the pituitary to govern all hormone production in the body, including: steroid hormones, thyroid hormones, growth hormones, and adrenal hormones.

Hypothalamus pituitary testicular axis (HPTA) – Known as the feedback loop from the testis to the hypothalamus and pituitary. The hypothalamus controls hormone production by sensing the level of hormones. For instance, when testosterone and estrogen are low, the hypothalamus senses this and releases gonadrotropin releasing hormone (GnRH), which stimulates the pituitary to release LH and FSH, which stimulates the testes to produce testosterone. When testosterone and estrogen are high, the release of GnRH is blunted, limiting hormone production.

Leydig cell – The cells within the testis which produce hormones (testosterone) in response to Luteinizing hormone.

IGF-1 – Also known as Insulin-like Growth Factor. IGF-1 is a polypeptide protein hormone with a similar structure to insulin and has powerful effects on the growth off all bodily cells, including muscle cells. IGF-1 is created in the liver by insulin and growth hormone. IGF-1 is also known to increase insulin sensitivity, whereas growth hormone is known to decrease insulin sensitivity. Maintaining a fair IGF-1 level positively influences hormone production within the gonads by stimulating CYP11A, 3b HSD, and StAR.(80,81,82) Insufficient levels of DHEA (or other androgens) are known to decrease IGF-1. (12,13)

Immunogenic – Creating immunity by activating of the immune system.

In vitro – In an artificial environment outside of a living organism.

In vivo – In a living organism. 

Luteinizing hormone (LH) – A hormone sent from the brain (pituitary gland) which stimulates the leydig cells within the testes to produce testosterone. Luteinizing hormone and follicle stimulating hormone act synergistically to support testosterone production and fertility.

Metabolite – Any substance which has been metabolized or altered from its original form. Eg., Testosterone is a metabolite of cholesterol.

Mitosis – The process of cell division where two identical cells are created.

Neurosteroid – Any steroid hormone which resides in the brain region, that influences behavior, memory, awareness, or general cognitive function.

Pituitary – A gland in the brain that receive signals from the hypothalamus to govern all hormone production in the body, including: steroid hormones, thyroid hormones, growth hormones, and adrenal hormones.

Precursor – A compound that turns into another compound. Cholesterol is precursor to testosterone.

Pregnenolone – A precursor to all hormones and a powerful neurosteroid positively effecting cognitive function and memory.(2,3) Pregnenolone Sulfate has also shown to stimulate GnRH release in the hypothalamus and modulate the release of LH and FSH from the pituitary further encouraging steroidal hormone production. (4)

Progesterone – While usually considered a female hormone, progesterone has important functions in the male body. By competing with testosterone for 5a-reductase progesterone helps to control DHT levels, which may support prostate health and prevent hair loss. (5) Anecdotal reports from male patients taking low-dose progesterone cream have also shown an increase in sexual pleasure and performance ability. (6)

Quinone – Quinones are toxic metabolites of estrogen which can form into carcinogenic substances which may damage DNA and promote cancer. (83,84)

5-alpha-reductase (5a-reductase) – An enzyme found mainly in the prostate and skin which serves to reduce the molecular structure of androgens. (converting androgens to “androstanes”)

Somatotrope – The cells within the pituitary gland which secrete growth hormone in response to growth hormone releasing hormone (GHRH) from the hypothalamus.

Somatostatin – An inhibiting hormone which inhibits growth hormone and thyroid stimulating hormone secretion from the pituitary.

Steroid acute regulatory protein (StAR) – The protein that carries cholesterol into the mitochondria of a cell to begin the conversion of cholesterol to pregnenolone. This step is generally considered the rate-limiting step in hormone synthesis.

Steroidogenic – Pertaining to the enzymes involved in the synthesis and metabolism of steroid hormones such as testosterone, estrogen, DHEA, cortisol, ect.

Testosterone – The primary male androgen. Similar to other androgens, testosterone can increase muscle mass and decrease fat mass by direct stimulation of protein synthesis. (49) Low testosterone is associated with depression, (50,51) bone loss, (52) heart disease, (53) and insulin resistance. (54) While testosterone plays a role in sexual function, many perceived effects of testosterone on sex drive and erectile function can be attributed more to the downstream metabolites such as DHT, androsterone, and estradiol(56,57)

Thermogenic/Thermogenesis – An increase in calorie expenditure, resulting in an increase in body temperature. Generally, thermogenics can help increase the burning of fat tissue by increasing energy expenditure.

Thyroid - The thyroid gland is located in the lower neck, and functions as the primary gland for thyroid hormone synthesis. T4, T3, and T2 are all thyroid hormones which influence carbohydrate, protein and fat metabolism. Maintaining healthy thyroid function is key for creating the optimum environment for muscle growth and fat loss.

Topical – A substance applied to the skin; as in, topical cream.

Transdermal – To absorb through the skin and enter the blood stream. Many topical creams act as a transdermal.

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