What is Androstenedione? Tests, Supplements, Side Effects

Androstenedione has few beneficial effects by itself – so why did it suddenly become one of the most popular sports supplements of the late 1990s? And why is it a banned substance now? Read on to learn more about the hormone they called Andro.

What Is Androstenedione?

Androstenedione is an androgen: a type of steroid hormone that promotes the development of male characteristics.

It is an intermediate “prohormone,” which means that it has weak effects on its own. Instead, androstenedione is used to produce testosterone and estrogen. The body can make it from either progesterone or dehydroepiandrosterone (DHEA) [1, 2].

Summary of the endogenous metabolism of cholesterol into multiple hormones. Some of the intermediaries are used as supplements to promote physical performance [3].

The compound that converts androstenedione into testosterone belongs to a group of enzymes called 17β-Hydroxysteroid dehydrogenases [2].

Function in Adrenarche and Puberty

Around the age of seven years old, children’s adrenal glands start to produce more and more DHEA. As a result, their skin produces more oil, their bones start to mature, and they develop body odor. This is considered an early phase of puberty or adrenarche, which translates to “the awakening of the adrenal gland.” Puberty is controlled by different mechanisms [4].

As DHEA increases, so does androstenedione. Children’s androstenedione levels rise from nearly nothing at the age of 4 to their lifetime peak around 18. Once they reach adulthood, their androstenedione levels begin to decline [5].

In adults, androstenedione is produced mainly by the ovaries and testes rather than the adrenal gland [6, 7].

Is Androstenedione Legal?

In March of 2004, the FDA unilaterally banned the sale of androstenedione supplements, declaring them “adulterated” products that pose health risks to users. Later that year, the US Congress passed the Anabolic Steroid Control Act of 2004, which officially declared androstenedione an anabolic steroid [8, 9].

Androstenedione is structurally more similar to other hormone precursors like DHEA, although it falls under the same group as all anabolic steroids [3].

Androstenedione is currently classified as a schedule III drug (under the Controlled Substance Act). This means its sale and use is completely banned. In the United States, androstenedione has the same legal status as ketamine. But unlike ketamine, androstenedione does not have any approved medical uses [10, 11].

In short: possession of androstenedione is considered a federal crime. We strongly recommend against using androstenedione for any reason.

Historical Uses

Androstenedione is illegal to buy, sell, or possess and therefore not available for supplemental use. The FDA banned it along with other anabolic steroids in 2004. We strongly recommend against using androstenedione for any reason.

Those who took it before it was reclassified as a steroid used it to increase testosterone, boost energy, and cut down on fat. Did it work? What was the cost?

1) Testosterone Levels

In one study, taking androstenedione boosted testosterone, but only at daily doses of 300 mg or above. After twelve weeks of supplementation, however, testosterone levels returned to their baseline. Meanwhile, estrogen levels also significantly increased [12].

The likely reason androstenedione raises estrogen levels is because it’s a steroid prohormone, which means that it can be aromatized into estrogen in the body [13].

In a group of older men that performed resistance training exercise, one week of androstenedione supplements increased the production of testosterone without increasing estrogen. The authors suggested that short bursts of androstenedione supplementation might help manage low testosterone in older men, but this has not been investigated further [14].

2) Boosting Energy

Those who take androstenedione to boost energy may be disappointed. Most studies have not found any increase in energy or athletic performance after supplementation with androstenedione [3, 15, 16].

3) Weight Loss

Androstenedione is unlikely to help you lose weight. In fact, by temporarily increasing testosterone, it may increase muscle mass without changing fat mass, leading to an overall increase in body weight. Over time, estrogen levels also rise, which may then increase fat mass [3, 12].

4) Osteoporosis

After menopause, women with osteoporosis have significantly lower blood levels of androstenedione than those who do not develop the disease [17].

Androstenedione levels, meanwhile, are closely related to estrogen levels: androstenedione is converted into testosterone, which is then converted to estrogen. Estrogen deficiency is believed to contribute to osteoporosis. In cell studies, androstenedione directly increases the activity of bone-building cells called osteoblasts [18, 19].

Researchers have only just begun to investigate the potential of androstenedione for osteoporosis [18].

Supplements Sold as “Andro”

In the wake of the FDA ban, supplement companies sold a variety of other muscle-building aids under the “andro” heading. These do not contain androstenedione, and their effects may vary. Most of these are “prohormone supplements:” compounds that are transformed into hormones in the body [20].

1-Andro

Perhaps the most common of the “andro” replacements, 1-andro is sold under many different names, including 1-androstenolone, 1-androsterone, 1-DHEA, and more. Its true chemical name is a mouthful: 3β-hydroxy-5α-androst-1-en-17-one [21].

Very little research has investigated the health effects of prohormone supplements like 1-andro. One study, however, found that 1-andro had both positive and negative effects. Participants experienced [20]:

• Increased lean body mass
• Decreased fat body mass
• Increased weight lifting capacity

But at the cost of:

• Decreased “good” HDL cholesterol
• Increased “bad” LDL cholesterol
• Damaged kidney function
• Damaged liver function

These supplements have not been approved by the FDA for any medical purpose or health claim, and we recommend strongly against using them.

4-Andro

Most supplements sold as “4-andro” claim to contain a chemical called 4-DHEA, which is very similar to the naturally occurring prohormone DHEA. 4-DHEA, which is also called 3β-Hydroxy-4-androsten-17-one, naturally occurs alongside DHEA in rats and humans [22, 23].

4-DHEA is not well studied, though related compounds have been shown to block aromatase and stop the body from converting testosterone to estrogen. Note that blocking aromatase may decrease both bone density and sexual function [24, 25].

These supplements have not been approved by the FDA for any medical purpose or health claim, and we recommend strongly against using them.

Andro400

This supplement does not claim to contain any andro compounds. Instead, its active ingredient is Eurycoma longifolia, or Tongkat Ali. This Southeast Asian medicinal herb activates the CYP17 enzyme (also called 17α-hydroxylase), which converts pregnenolone and progesterone into DHEA and androstenedione. Clinical studies have also demonstrated that Tongkat Ali increases testosterone in the blood [25, 26, 27].

Thus, while Andro400 does not contain any androstenedione or testosterone, it may encourage your body to make more of its own. We strongly recommend talking to your doctor before trying Andro400.

Androstenedione Safety & Side Effects

The most consistent side effect of androstenedione is a poor cholesterol profile: over time, supplementation decreases good cholesterol and increases bad cholesterol [28].

According to a long-term study of mice and rats, androstenedione supplements increase the risk of liver and pancreatic cancers; they may also damage the kidneys, clitoral gland, and salivary glands. However, this hormone may also decrease the risk of malignant lymphoma and of non-cancerous tumors in the testicles and breasts [29].

Androstenedione seems more likely to cause liver cancer in men than in women [30].

Supplementation with androstenedione increases both testosterone and estrogen. As a result, men may experience breast tissue growth (gynecomastia), erectile dysfunction, low sperm count, and poor cholesterol ratios over the long term [31].

In women, androstenedione may increase body hair growth and increase abdominal fat. Other changes, such as a lowered voice pitch, are also possible [28].

Drug Interactions

Very little research suggests any specific drug interactions between androstenedione and drugs. As such, this is not a complete list of possible interactions. However, we can find some clues about potential interactions in its safety profile and side effects.

Androstenedione supplements decrease good (HDL) cholesterol and increase bad (LDL) cholesterol. High-dose diuretics, amiodarone, some diabetes medications, antipsychotic medications, immunosuppressants, and antiviral drugs can also increase LDL cholesterol and may worsen this effect [28, 32].

In addition, androstenedione may damage the kidney and liver. A huge variety of drugs may also contribute to kidney and liver damage; combining androstenedione with most medication may increase these risks [29, 33, 34].

What’s more, it can affect the efficacy of many hormonal (or hormone-blocking) therapies due to its effects on sex hormone levels.

While no specific interactions between androstenedione and medication have been studied, this hormone has a high risk of potential interactions with numerous other compounds.

Memory Loss with Age

Before menopause, the most important ovarian hormone is estrogen; after menopause, it is androstenedione. This switch is thought to be partially responsible for age-related memory loss in women [6].

A mouse study revealed that estrone, not androstenedione, may be the true culprit. When researchers blocked the enzyme that converts androstenedione to estrone (aromatase), the memory problems improved. However, this has not been replicated in humans [6].

Diseases with High Androstenedione

Polycystic Ovarian Syndrome

Polycystic ovarian syndrome, or PCOS, is a very common hormonal disorder affecting up to 15% of adult women. Women with PCOS usually suffer from disordered ovulation, high levels of androgens like testosterone, and cysts on their ovaries. As a result, they are prone to excessive body hair, chronic inflammation, obesity, insulin resistance, and type 2 diabetes [35].

Women with PCOS have higher than normal blood levels of androstenedione; this abnormality can sometimes be used to identify the syndrome [36].

In particular, two metrics may predict whether someone with PCOS is likely to develop insulin resistance and diabetes: total androstenedione and the ratio between androstenedione and free testosterone [37, 38].

When measuring androstenedione alone, higher levels predict insulin resistance. In combination, higher androstenedione relative to free testosterone appears to be protective [37, 38].

Women with PCOS have more androstenedione in their uterine tissues, which may contribute to a high risk of endometrial cancer. Strangely, baby girls born to mothers with PCOS had less androstenedione in their umbilical cord blood compared to the children of unaffected women [39, 40].

Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia, or CAH, is any one of a family of genetic disorders affecting the adrenal glands. In all cases of CAH, some step in the transformation of cholesterol into its steroid products is disrupted [41].

The androstenedione blood test is one of a series used to diagnose CAH in infants, with a high androstenedione result indicative of the most common type of CAH [42, 41].

Androstenedione Test

Androstenedione can be measured directly from a blood sample [42].

Normal Range for Adult Men

According to the Endocrine Society, which manages multiple journals on endocrine research, adult men should have androstenedione levels in the range of 65–210 ng/dL or 2.27–7.33 nmol/L.

These levels will decrease with age, and the highest numbers are only expected for young adults shortly after adolescence [43, 44].

Normal Range for Adult Women

According to the Endocrine Society, adult women should have androstenedione levels in the range of 80–240 ng/dL or 2.79–8.38 nmol/L. However, other studies of healthy women have found androstenedione levels range from 0.89 to 4.56 nmol/L. As is the case for men, these levels will decrease with age [43, 45].

Higher androstenedione levels are normal in younger women, but test results outside the reference range may be a sign of polycystic ovarian syndrome (PCOS) [46].

Children and Adolescents

Children undergo a dramatic swing in androstenedione from birth to adulthood.

Levels are as high as 10.1 nmol/L at birth (average of 3.8 nmol/L for girls and 5.6 nmol/L for boys). Between 2 and 4 months, average androstenedione is 1.4 nmol/L; between 4 and 12 months, it drops to 0.4 nmol/L [5, 47].

By the age of 8 years, androstenedione levels rise back up to around 1 nmol/L. They continue to rise through puberty, reaching a peak of as high as 10.9 nmol/L [5, 47].

In children, androstenedione tests are used to check for high androgen production in girls. It is also part of a series of tests to identify a condition called congenital adrenal hyperplasia [42].

Factors that Increase Androstenedione

Most importantly, work with your doctor to treat any underlying conditions causing your low androstenedione levels. You may try the additional strategies listed below if you and your doctor determine that they could be appropriate. None of these strategies should ever be done in place of what your doctor recommends or prescribes.

Exercise

Exercise significantly increases androstenedione in men more significantly than in women. However, this change may be at the expense of testosterone, which falls during exercise for most people. Only very fit athletes avoid a drop in testosterone during exercise [48, 49, 50, 51].

Together, these results suggest that the best natural ways to increase androstenedione without dropping testosterone would be to improve overall fitness and exercise frequently.

Diet

A diet higher in fat may prevent declines in androstenedione and free testosterone.

One clinical study observed a group of middle-aged men whose usual diets provided 40% of energy in the form of fats. When they changed these diets so that fat only provided 25% of their calories, their androstenedione and free testosterone levels dropped [52].

It’s important to be very mindful of the type of fat you consume on a higher-fat/keto diet. In general, avoiding excess saturated fats is vital for overall wellness.

Additionally, a regular circadian rhythm and enough protein in your diet are also important.

In one study, rats with a disturbed circadian rhythm (kept in constant darkness) produced less androstenedione. But these effects were less severe in rats fed normal amounts of protein than in those fed low-protein diets [53].

High-fiber diets also decrease androstenedione, one reason why they are recommended to women with PCOS. This suggests that reducing fiber intake may increase androstenedione; however, dietary fiber has many other positive health effects [54, 55].

We do not fully understand the effect of diet on androstenedione, but certain changes may increase its production. Overall, these include a higher percentage of energy provided by fats (as opposed to sugars) and increased protein intake.

Genetics

Androstenedione genetics are not well studied. However, researchers have identified a handful of genes that affect how much androstenedione you naturally have in your body.

• TNFSF9 produces an inflammatory protein called 4-1BB ligand. At rs348373, the T allele is associated with increased androstenedione [56, 57].
• CYP17A1 produces an enzyme that is vital for your body to make androstenedione. At rs743572, people with two copies of the C allele may have lower androstenedione. This relationship is currently in dispute, with differing results in Japanese and British populations [58].
• CYP19 produces aromatase, which converts testosterone to estrogen and androstenedione to estrone. Many variations in CYP19 affect androstenedione, but the exact relationships are currently unknown. Women with PCOS tend to have unusual CYP19 variations [59, 60].

Limitations and Caveats

Androstenedione was at its most popular among scientists and athletes in the late 1990s and early 2000s. After the FDA ban and its reclassification as an anabolic steroid, research on androstenedione slowed down. It has only recently been considered a possible drug target for various diseases, including PCOS and osteoporosis; thus, researchers have regained some interest in this topic.

Many “testosterone-boosting” supplements use the word “andro” to harken back to the heyday of supplementation with androstenedione. To make matters even more confusing, these supplements often use unscientific or even completely fabricated names for the chemicals in their products. There is currently not enough research on these supplements to know exactly what is in them, let alone whether they are effective.

Increased androstenedione has different effects on the male and female body. Research on men may not apply to women and vice versa. Furthermore, research on women with PCOS may not apply to women without, and vice versa.