Androgens & Androgen Deficiency

The sex hormones are divided into two major groups, androgens and estrogens (oestrogens.) Traditionally, androgens where considered to be the "male" sex hormones and estrogens the "female" sex hormones, but both play an active and vital role in the normal function of both sexes. There are three types of estrogen that have a role in over 400 bodily functions. The three types of estrogen are estrone (E1), estradiol (E2), and estriol (E3). There are five types of androgens that influence a woman’s sexual desire, mood, and energy, and they are necessary for healthy bones and muscles. The five types of androgens are dihydrotestosterone (DHT), testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and androstenedione. The total amount of androgens in women is estimated to be about 71% of that of men, which is a level much greater than previously believed.

Androgen levels first start to increase between the ages of six and ten but do not reach their maximum levels until between the ages of 20 and 30. The onset of increased androgen production is referred to as adrenarche. The first visible indication of this event is the development of pubic hair, which is referred to as pubarche. The increasing level of these hormones at this young age is a possible reason why 47% of women report they experienced sexual desire prior to their first menstrual period, menarche. Menarche is unrelated to andrenarche, and a woman can experience the onset of menstruation without ever developing pubic hair. The fact that androgen levels do not peak until a woman is in her twenties may explain why 68% of women report their level of sexual desire is greater in their twenties than their teens, and why some do not experience the onset of intense sexual desire until they are in their late teens or early twenties. When a woman's level of androgen decrease to 10-20% of their peak level it is referred to as adrenopause, which is independent of menopause.

Androgens are initially produced by the ovaries and adrenal glands. After being produced by these organs they enter the blood stream and circulate throughout the body to the tissues and organs that are sensitive to and controlled by them. The amount of estrogens and androgens in the blood, for the most part, indicate the amount of these hormones being produced by the ovaries and adrenals, but these levels do not accurately indicate the amount of these hormones in the tissues of the body. The level of these hormones in the blood indicate the general health, menstrual state, and functional age of the ovaries and adrenals.

Relatively recently it was discovered that the conversion of hormones into other types of hormones takes place within the individual cells that use them. As an example, the hormone DHEA is converted into testosterone during a chain of events inside some cells within the tissues of the breast, and other organs. It is now believed that the majority of the testosterone produced and consumed within the female body is done in this manner. These newly converted hormones are consumed by the cell and only the bi-products of that process enter the blood stream.

Only a small fraction of the hormones produced within the cells of the different organs enter into the blood stream where they can be measured by standard blood tests. The amount of androgen in the tissues is measured indirectly through the amount of bi-product within the blood. To determine the total amount of androgens in the body the amount of androsterone glucuronide (ADT-G), androstenediol glucuronide (3α-diol-G), and androsterone-3β (3β-diol-G) in the blood must be measured. The most reliable test methods employ radioimmunoassays; some luminometric assays are reported to be "problematic."

As indicated by the following graphs and tables, the amount of androgens in the blood stream decrease throughout adulthood, and have decreased significantly by the completion of menopause. While the androgen output of the ovaries may have decreased during menopause they do not reduced to zero. This is demonstrated by the fact that postmenopausal women who have had their ovaries surgically removed have significantly lower levels of androgens than women who did not.

Total Testosterone

Age

18-24

25-34

35-44

45-54

55-64

65-75

55-64 *

65-75 *

Mean Total Testosterone Level nmol/liter

1.58

1.11

0.92

0.81

0.66

0.71

0.38

0.39

* After surgical removal of ovaries

Free Testosterone

Age

18-24

25-34

35-44

45-54

55-64

65-75

55-64 *

65-75 *

Mean Free Testosterone Level pmol/liter

23.61

17.25

13.67

11.82

10.81

9.76

5.54

6.06

* After surgical removal of ovaries

DHEAS

Age

18-24

25-34

35-44

45-54

55-64

65-75

55-64 *

65-75 *

Mean DHEAS Level μmol/liter

7.49

4.72

4.31

3.42

2.36

1.76

1.89

1.13

* After surgical removal of ovaries

Androstenedione

Age

18-24

25-34

35-44

45-54

55-64

65-75

55-64 *

65-75 *

Mean Androstenedione Level nmol/liter

8.46

6.44

5.15

4.17

3.14

3.07

2.15

2.93

* After surgical removal of ovaries

Hormone

% Decline Over Full Age Range

Total Testosterone

55

Free Testosterone

49

DHEAS

77

Androstenedione

64

The data presented in the above graphs and tables came from the article Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy The Journal of Clinical Endocrinology & Metabolism 90(7):384-3853 April 12, 2005

The following illustrations reveal how much the ovaries contribute to the amount of androstenedione and testosterone in the blood prior to and after menopause. They also show how some of the DHEA that is converted into androstenedione and testosterone within the cells of the body contributes to the amount of these hormones in the blood.

Prior to menopause the ovaries contribute 50% of the androstenedione present in the blood. Women who have had their ovaries removed prior to menopause may experience a 50% decrease in the amount of androstenedione in their blood, but this may not cause a significant change in the overall amount of androstenedione in their body.

After menopause the ovaries contribute 20% of the androstenedione present in the blood. Women who have had their ovaries removed after menopause may experience a 20% decrease in the amount of androstenedione in their blood, but this may not cause a significant change in the overall amount of androstenedione in their body.

The ovaries contribute about half of the amount of testosterone in the blood throughout a woman's lifetime. Surgical removal of the ovaries may result in a 50% decrease in the amount of testosterone present in the blood, but this may not cause a significant change in the overall amount of testosterone in the body. The amount of testosterone in the blood decreases by about 50% between the ages of 21 and 40. This is thought to be the result of the declining level of DHEA produced by the adrenals.

The following illustration demonstrates how only 10% of the testosterone present in the tissues of the body originates in the blood stream. The remaining 90% is the result of the conversion of DHEA to testosterone within the cells. DHEA must be converted into other hormones prior to its conversion into testosterone. When testosterone is converted into DHT it is most effective.

The information contained in the four illustrations shown above came from the article Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursors. Endocrine Reviews 24(2): 152-182 Copyright 2003

Androgen Deficiency

There is no agreement amongst the medical community concerning what constitutes androgen deficiency in women and its roll in sexual dissatisfaction.

The Princeton consensus in 2002 defined it as when a woman meets all three of the following conditions:

1. She believes she is experiencing impaired well-being or libido
2. She has adequate estrogen levels, meaning her ovaries are producing sufficient estrogen or she is on estrogen replacement therapy (ERT)
3. She has blood levels of androgens that are less than or equal to 25% of the normal or average amount. If the average amount is 100, then measured values of 0-25 meet this condition.

The Sexual Function Health Council of the American Foundation for Urologic Disease (AFUD) defined Hyposexual Desire Disorder (HSDD) as when the following two conditions exist at the same time:

1. Continuous or recurrent experiences of decreased frequency of or absent sexual fantasies, thoughts and/or desire for or willingness to engage in sexual activity. Basically, little or no sexual feelings or motivations.
2. The existence of the first condition leads to person distress. Meaning you are very unhappy because you are not experiencing sexual feelings or desires as often as you would like or believe you should.

Some find fault with the use of any condition that cannot be verified in a medical lab with proven tests and verifiable results, which is any condition a women determines for herself. Since medical science has not found a clear link between the majority of self reported cases of low sexual desire and measurable androgen deficiencies this is to be expected. Though women are understandably frustrated by the medical community's apparent lack of action when it comes to resolving their lack of sexual desire.

One study found that having low DHEAS levels did not automatically lead to women reporting lower sexual satisfaction, but women who reported having impaired sexual function were more likely to have a low DHEAS level. The question becomes, do some women experience decreased sexual desire without knowing or are low DHEAS levels unrelated to sexual desire? Keep in mind that in the past, and to varying degrees today, society said women don't experience innate sexual desire, that they engage in sex for purely non-sexual motives; love, partner's needs, intimacy, etc. This means women may not be concerned with an absence of purely sexual motives. Women may also expect their desire for sex to decrease with age and their decreased desire is to be expected and is normal, and therefore not a problem; it just is. If sexual desire leads to sex and pregnancy and more children you may be happy to no longer experience it. If sexual desire leads to sexual frustration you may be more than happy to do without. A woman may not believe she is experiencing decreased sexual desire until outside forces, partner's sexual demands and the mass media, lead her to believe so. These factors may explain why women and their doctors do not agree when it comes to explaining and treating sexual dissatisfaction, and specifically low sexual desire.

Why then do women routinely experience increased sexual desire when they are prescribed androgens, specifically testosterone? One possible answer is the fact that the prescribed dosages often raised a woman's level of testosterone to above average levels; lower dosages do not appear to have the same affect. It seems possible that you can raise a woman's level of sexual desire to a point that it overcomes other factors that are the true cause for the low desire, specifically environmental factors. If you ring a woman's sexual bell loud enough she cannot help but hear it. This scenario becomes a real possibility when one considers the fact that women frequently do not perceive their true level of physical sexual arousal when they are exposed to sexual stimulus. The problem with too much testosterone is that it has undesired side affects.

The following is a list of conditions and causes that may lead to some degree of androgen deficiency.

Low androgen levels may be indicated by:

- Diminished feelings of well-being
- Lethargy (exhaustion, low energy)
- Loss of sex drive and interest
- Unexplained fatigue
- Reduced motivation, pubic hair, and bone and muscle mass
- Poor quality of life
- Problems with blood vessel constriction and dilation
- Insomnia
- Depression
- Headaches

Low androgen levels may be caused by:

- Increasing age²
- Low ovarian output caused by medical factors or surgical removal of the ovaries
- Low adrenal gland output
- Hypopituitarism²
- Glucocorticoid therapy² (Used to treat asthma and rheumatic diseases.)
- Use of oral contraceptives and oral estrogens²- Addison's disease⁴
- Corticosteroid therapy⁴
- Chronic illness⁴
- Chronic stress⁶
- Estrogen replacement (leads to elevated SHBG and, therefore, low free testosterone)⁴
- Premenopausal ovarian failure⁴
- Oophorectomy⁴ (Removal of the ovaries)
- Progestin; cyproterone or drospirenone used in oral contraceptives⁶

Low androgen levels may be associated with³:

- Osteoporosis
- Obesity
- Type 2 diabetes
- Sexual dysfunction
- Loss of muscular strength
- Turner's syndrome⁶

Treatment of Androgen Deficiency

It is now believed that decreasing DHEA levels may account for some of the symptoms associated with androgen deficiency rather than the measurable decrease in the other four types of androgens in the blood. This is because the amount androgens in the blood does not accurately reflect the total amount of androgens in the tissues of the body. This may explain why current research has not found a clear correlation between the amount of androgens in the blood and female sexual dissatisfaction. I am not aware of research that has looked for or found a specific correlation between DHEA and sexual dissatisfaction, as of November 2006.

Studies have found that when women experiencing adrenal insufficiency took 50mg of DHEA daily it brought their levels of androgens and estrogens up to normal premenopausal levels, "without significant side affects." DHEA can also be administered in the form of a topical cream. DHEA is available without a prescription but such products are not under Food and Drug Administration (FDA) control. A study conducted in 1998 found that over the counter products that were said to contain 25mg of DHEA actually had anywhere between 0 and 140 mg; partial testing results from 2006 can be seen by clicking here. If a woman chooses to take DHEA, it is highly advisable for her to consult her doctor so they can monitor her hormone levels to ensure they increase to the desired levels without becoming too high. The use of DHEA is believed to avoid some of the adverse side affects associated with Estrogen Replacement Therapy (ERT) and Hormone Replacement Therapy (HRT), because the resulting increased hormone levels in the tissues are not circulating throughout the body in the blood stream where they can affect tissues and organs in undesired ways. I would caution women against taking DHEA unless laboratory testing has indicated their androgen levels are significantly lower than they should be.

You can learn more about DHEA, as a medical treatment, at the following web sites:

http://www.mayoclinic.com/health/dhea/NS_patient-dhea

http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-dhea.html

References:

1 Assessment and Management of Women's Sexual Dysfunctions: Problematic Desire and Arousal. The Journal of Sexual Medicine Volume 2 Number 3 2005

2 A clinical update on female androgen insufficiency-testosterone testing and treatment in women presenting with low sexual desire. Sex Health. 2006 May;3(2):73-8.

3 Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women. The Journal of Steroid Biochemistry and Molecular Biology. 2006 Jun;99(4-5):182-8.

4 Androgen production in women. Fertility and Sterility 2002 Apr; 77 Supplement 4:S3-5

5 Menstrual cycle irregularities are associated with testosterone levels in healthy premenopausal women. Am J Hum Biol. 2006 Nov-Dec;18(6):841-4

6 Androgen Therapy in Women European Journal of Endocrinology 2006 154 1-11 See Text File or PDF File

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursors. Endocrine Reviews 24(2): 152-182 Copyright 2003. See Text File or PDF File

Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy The Journal of Clinical Endocrinology & Metabolism 90(7):384-3853 April 12, 2005. See PDF File

Hormone	% Decline Over Full Age Range
Total Testosterone	55
Free Testosterone	49
DHEAS	77
Androstenedione	64