When Total Testosterone Is Normal: Could Other Androgens Reveal More About PCOS/PMOS?

First, What Are Androstenedione And DHEAS?

Androgens are a group of hormones that includes:

• Testosterone
• Androstenedione
• DHEAS

In PCOS/PMOS, higher androgen activity can be associated with concerns such as:

• Acne
• Increased facial or body hair
• Scalp hair thinning
• Irregular cycles
• Difficulty ovulating

These symptoms can be influenced by many factors, and blood levels do not always perfectly reflect what someone experiences. However, androgen testing can form one part of a broader PCOS/PMOS assessment.

The Researchers Compared Different Ways Of Assessing Androgens

The researchers began with a practical baseline assessment using:

• Documented hirsutism, meaning increased coarse facial or body hair
• Total testosterone

They then looked at what happened when they added:

• Androstenedione
• DHEAS
• Both androstenedione and DHEAS

Each time an additional hormone was included, the researchers recalculated whether the women would be classified as having hyperandrogenism and whether their PCOS classification or PCOS phenotype would change.

Broader Testing Identified More Women With Hyperandrogenism

Using documented hirsutism and total testosterone alone, 86.8% of the women were classified as having hyperandrogenism.

When androstenedione and DHEAS were both included, this increased to 93.2%.

In total, an additional 28 women, or 6.4% of the study group, were classified as hyperandrogenic when the broader hormone panel was considered.

This supports the importance of looking at the broader androgen picture, particularly when symptoms and total testosterone results do not seem to match.

A Normal Total Testosterone Result Did Not Always Mean All Androgens Were Normal

Of the 207 women whose total testosterone was within the laboratory reference range:

• 38.6% had elevated androstenedione
• 16.9% had elevated DHEAS
• 47.3% had an elevation in at least one of these additional androgens

This is one of the most interesting findings from the study.

It reinforces that a normal total testosterone result does not necessarily mean every androgen marker will also be within range.

This does not automatically confirm PCOS/PMOS, but it may help explain why some women experience signs of higher androgen activity despite having normal total testosterone results.

Androstenedione Added More Information Than DHEAS

Androstenedione had a greater effect on classification than DHEAS.

An isolated elevation in androstenedione was found in 14.4% of the women, compared with an isolated DHEAS elevation in 4.1%.

Adding androstenedione changed the assigned PCOS phenotype in 4.3% of the study group, while adding DHEAS alone changed it in 1.8%.

This does not mean androstenedione is a better diagnostic test in every situation. It simply means that, within this particular group of women, it contributed more additional classification information than DHEAS.

The Overall PCOS Classification Changed Less Dramatically

While the broader hormone panel identified more women with hyperandrogenism, it had a smaller effect on who was classified as having PCOS.

PCOS classification increased from:

72.8% using hirsutism and total testosterone

to:

75.6% when androstenedione and DHEAS were also included

This meant that 12 of the 438 women, or 2.7%, moved from being classified as non-PCOS to PCOS when the additional androgens were considered.

The smaller change makes sense because androgen excess is only one part of the Rotterdam diagnostic framework.

A PCOS diagnosis generally requires at least two of the following three features:

• Irregular or absent ovulation
• Clinical or biochemical hyperandrogenism
• Polycystic ovarian morphology

Changing one part of this picture will not necessarily change the overall classification if the other diagnostic features are not present.

Additional Testing Had A Bigger Effect On PCOS Phenotypes

The Rotterdam framework can also be used to group PCOS into different phenotypes depending on which combination of features is present.

When androstenedione and DHEAS were added, the assigned phenotype changed in 24 women, or 5.5% of the study group.

Some women who had previously been classified as having a non-hyperandrogenic phenotype were moved into a hyperandrogenic phenotype. Others who had not previously met the study’s PCOS classification moved into a PCOS phenotype.

This is important because the hormones included in testing may influence not only whether someone is classified as having PCOS, but also how their individual presentation is described.

However, the study did not investigate whether these classification changes affected symptoms, treatment response, fertility or long-term metabolic health.

The Difference Was Greatest When Hirsutism And High Testosterone Were Both Absent

The researchers also looked more closely at 58 women who did not have documented hirsutism and whose total testosterone was normal.

Within this smaller group:

• 48.3% had elevated androstenedione and/or DHEAS
• 20.7% moved from a non-PCOS classification to PCOS
• 41.4% had a change in their assigned PCOS phenotype

These results suggest that additional androgen testing may provide the most new information when obvious clinical signs of androgen excess are absent and total testosterone is normal.

However, this was an exploratory analysis in a relatively small subgroup, so it should be interpreted cautiously.

This Does Not Mean Everyone Needs Every Androgen Tested

The study measured how often additional tests changed the researchers’ classification. It did not prove that broader testing produced a more accurate diagnosis.

This distinction is important.

The baseline assessment did not include free testosterone or sex hormone-binding globulin, also known as SHBG. This means it did not represent the complete first-line biochemical androgen assessment recommended in current guidelines.

The study was also retrospective, came from a single endocrine clinic and included women who were already being evaluated for PCOS or related symptoms. This means the results may not apply in exactly the same way to the general population.

The researchers also used laboratory immunoassays and laboratory-specific reference ranges, so results may differ with other testing methods or reference ranges.

What Does This Mean For PCOS/PMOS?

The most useful takeaway is that androgen assessment can be more complex than looking at one total testosterone result.

A normal total testosterone result does not automatically rule out other biochemical androgen changes. In this study, androstenedione provided more additional classification information than DHEAS, particularly among women whose total testosterone was normal.

At the same time, these hormones should not be interpreted in isolation.

Symptoms, menstrual patterns, ovulation, ovarian morphology, medications, age, testing methods and the exclusion of other possible conditions all form part of a complete assessment.

This research does not suggest that every woman requires an extensive hormone panel. It does support considering the broader androgen picture when symptoms and initial blood results do not appear to match.