Saliva testing for hormonal diagnosis: The facts and basics

For decades, female hormone levels were measured using blood tests.¹ But blood sampling is invasive, expensive and is, at times, logistically difficult. Hence, there was a shift towards more convenient and inexpensive sample types like saliva.

Saliva-based tests are highly precise and painless. They are a reliable and proven method for evaluating female hormone levels.¹

This article sheds light on how saliva testing for female hormone imbalance is revolutionizing the clinical diagnostics landscape and positively influencing women’s health globally.

Saliva testing is a sensitive, cost-effective method to diagnose a hormonal imbalance at any stage of a woman’s life. Image Credit: Tecan

Why is it important to measure female hormone levels?

The mere mention of female hormone levels elicits a complete spectrum of conditions that the medical profession recognizes as being real and treatable.

Be it the heartbreak of infertility, dealing with the subjective mood and body changes linked to premenstrual syndrome, or being healthy through menopause, controlling hormone imbalance is vital and can be a major contributor to a woman’s quality of life.^2–4

Which female hormones are measured?

Hormone imbalance is the major reason why women experience the symptoms, syndromes and diseases throughout their reproductive years. These imbalances can be evaluated and treated by directly administering the lacking hormones or their equivalent precursors.⁵

Hormone treatments are mostly provided along with recommendations on lifestyle changes, like exercise and diet, to enhance or retain physical and cognitive health.

Steroid pathways

Figure 1 illustrates a simplified version of the interrelations between the various hormonal pathways in women.

An evaluation of a selection of hormones in these pathways would provide the physician a signal of hormone imbalance, resulting in a recommended course of treatment.

Figure 1. Steroid pathways. Image Credit: Tecan

For a woman who suffers from a diagnosed hormone imbalance, simple medicinal adjustments along with lifestyle changes make a drastic difference.

For instance, throughout her reproductive years, a woman might suffer greatly from symptoms linked to period-related problems, like excessive bleeding, or premenstrual syndrome (PMS), which compromises her quality of life.⁶

The majority of the women experience PMS at a certain point in their lives, and in about 30% of the women worldwide, these symptoms adversely affect their daily activities.⁶

The menstrual cycle is driven by different hormones: the female sex hormone estrogen regulates the maturation of an egg cell every month while the hormone progesterone prepares the lining of the womb for a possible pregnancy.

Along with other treatments like nonsteroidal anti-inflammatory drugs (NSAIDs) to help reduce pain, progesterone can also be employed to decrease menstrual bleeding, and enhance mood, as a “natural” antidepressant in cases of severe PMS, however, its use in PMS is still controversial.^7,8

The estrogen group includes three major hormones: estriol, estradiol and estrone (Fig.1).

The major circulating estrogens are estriol at the time of pregnancy, and estrone at the time of menopause. Estradiol is the major estrogen during the reproductive years relating to absolute serum levels and estrogenic activity.

Women can benefit from menstrual cycle mapping throughout their reproductive years and into menopause.

This could entail taking samples on a daily basis to track fluctuating hormone levels and, as a result, pinpoint hormone imbalances more precisely than would be possible with a single or small number of sampling points.

As it is much easier to collect saliva samples daily than it is to collect blood samples, the introduction of saliva testing has made accurate mapping more possible.

When a woman reaches perimenopause and then menopause, the question of whether hormone replacement therapy (HRT) is beneficial or harmful to her health rages on.⁵

The answer is a resounding “it depends,” and a practitioner will make a recommendation based on a patient’s unique health history.

Most menopausal symptoms, such as hot flashes, night sweats, mood swings, vaginal dryness and reduced libido, can be alleviated with HRT.⁹ It can also help prevent bone thinning (osteoporosis), which is more common after menopause.¹⁰

Many of these symptoms fade away after a few years, but they can be unpleasant, and HRT can help many women.

Although the benefits of HRT are generally thought to outweigh the risks, one disadvantage is that some types of HRT can increase the risk of breast cancer, so if a woman has a family history of cancer, she may prefer to avoid taking the risk and simply ride out the menopausal symptoms instead.⁹

Hormonal imbalance is also one of the leading causes of female infertility, and after the age of 35, a woman's fertility naturally declines due to changing hormone levels.¹¹ Decreased levels of luteinizing hormone (LH), which stimulates the ovaries to release an egg and begin producing progesterone, also cause fertility issues.

High levels of follicle-stimulating hormone (FSH) decrease a woman’s chance of getting pregnant. Fertility is also affected by early menopause and other hormone-related conditions such as PCOS (polycystic ovary syndrome).

To validate a diagnosis of hormone imbalance, the physician first establishes the levels of the relevant hormones.

But how is this carried out and what are the recent trends towards a holistic and personalized approach to women’s health?

Measuring female hormone imbalance

After the symptoms of a potential hormone imbalance have been identified, like infertility, or hot flashes in menopause, the physician would initially evaluate the level of specific hormones.

Normally blood samples are drawn and serum-based tests will be carried out. But, the search for inexpensive and less invasive means for measuring female hormones led scientists to investigate if saliva would be a viable alternative, and thus saliva-based ELISA hormone testing was created.¹²

While developing new tests, the results of the tests replacing blood sampling should be as precise as the equivalent blood tests, and ELISA-based saliva testing proved to be a reliable method for female sex hormone testing.

ELISA is precise and affordable along with being painless and convenient for the patient.¹³

Advantages of saliva-based testing

Along with being non-invasive and inexpensive, this technique also has other advantages like performing the test anywhere at any time and the fact that multiple specimens can be collected. Moreover, saliva samples are also easy to store when compared to blood samples.

In comparison to blood or urinary steroids, salivary steroids more precisely depict the biologically active hormones in the body (Fig. 2).

Figure 2. Steroids in blood and saliva: the case for saliva testing. Image Credit: Tecan

Even with these results, physicians are still hesitating when it comes to recommending saliva testing.

The predominance of blood testing and the hurdles in replacing already established assays might be a reason for this. However, despite this, there is a surge towards saliva testing, as depicted by the advancing market figures.

The market for female hormone testing

An overview of the global prevalence of these issues can provide some indication of how many women may consult and be tested at some point during their lives, based on the major application areas outlined above, namely hormone imbalance associated with menstruation, menopause and infertility.

Local healthcare infrastructure and cultural issues must also be considered, as they will have an impact on the number of women who seek treatment and are able to do so.

In a systematic review, it was discovered that the global prevalence of PMS was 47.8%. However, only about 3–5% of the estimated 1.9 billion women of reproductive age will have severe enough symptoms (or the financial means) to seek medical help or self-refer and purchase tests online.^15–22

Even if only 1% of women sought help and received treatment, this equates to roughly 20 million individual tests per year.

Infertility affects an estimated 15% of couples worldwide, totalling 48.5 million couples. Male infertility accounts for about 20–30% of all infertility cases, accounting for 50% of all cases.^23,24

Couples who are having difficulty conceiving will require a series of comprehensive hormone tests, whether for diagnosis or treatment. These tests could be blood- or saliva-based.

Tests for menstrual, menopausal and fertility-related issues can also be purchased over the counter or online. Blood and saliva are the most common sample types, with saliva tests becoming more common.^13,14

Furthermore, in the developed world, the 24/7 online culture means that the world is more self-aware, with a trend toward taking personal responsibility for health problems and using the internet to self-diagnose.

The saliva-based point of care (POC) market for measuring hormone levels is exploding as a result of this.

Blood to spit: Make the switch

Saliva-based testing is a safe and reliable alternative to blood tests, and as a result, it is gaining popularity in a variety of fields, including female hormone testing.

References

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13. Belkien, L. D., Bordt, J., Möller, P., Hano, R., & Nieschlag, E. (1985). Estradiol in saliva for monitoring follicular stimulation in an in vitro fertilization program. Fertility and sterility, 44(3), 322–327. PubMed ID: https://pubmed.ncbi.nlm.nih.gov/4029421/ DOI: https://doi.org/10.1016/s0015-0282(16)48855-2
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