DUTCH Plus®

The DUTCH Plus^® takes hormone testing to a whole new level. In addition to sex hormones and their metabolites, the DUTCH Complete™ looks at the overall diurnal pattern of free cortisol, and the total and distribution of cortisol metabolites. The DUTCH Plus^® adds the Cortisol Awakening Response (CAR) to bring another important piece of the HPA-axis into focus.

What is the Cortisol Awakening Response and how do we test for it?

When we open our eyes upon waking, cortisol levels naturally begin to rise by an average of 50%. 30 minutes after waking, cortisol levels will still show this sharp increase. By 60 minutes after waking, cortisol levels have peaked and begin to decline. Measuring this rise and fall of cortisol levels at waking can be used as a “mini stress test”. Research shows that the size of this increase correlates with HPA-axis function, even if the sample measurements are all within range. A quick saturation of saliva swabs upon waking, and at 30 and 60 minutes after waking, provide what is required to assess a patient’s Cortisol Awakening Response.

A low or blunted Cortisol Awakening Response

This can be a result of an underactive HPA axis, excessive psychological burnout, seasonal affective disorder (SAD), sleep apnea or poor sleep in general, PTSD, chronic fatigue and/or chronic pain. A decreased CAR has also been associated with systemic hypertension, functional GI diseases, postpartum depression, and autoimmune diseases.

An elevated Cortisol Awakening Response

This can be a result of an over-reactive HPA axis, ongoing job-related stress (anticipatory stress for the day), glycemic dysregulation, pain (i.e. waking with painful joints or a migraine), and general depression (not SAD). A recent study1 showed that neither the waking nor post-waking cortisol results correlated to Major Depressive Disorder, but the CAR calculation (the change between the first two samples) did. This measurement of the response to waking has independent clinical value showing dysfunction that may be hidden by current testing options.

What’s Included in the DUTCH Plus^®

The DUTCH Plus^® uses four dried urine samples and five saliva samples. These samples are collected over the course of one day, from waking to bed time. The DUTCH Plus^® report includes: Metabolites of Estrogens (10, including E1, E2, E3, 2-OHE1, 4-OH-E1, 2-OH-E2, 4-OH-E2, 16-OH-E1, 2-methoxy-E1, 2-methoxy-E2) , Androgens (8, including Testosterone, DHT and DHEA-S), Progesterone (2), Cortisol (3), Melatonin (6OHMS), 8-OHdG, and OATs (6). The diurnal pattern of Free Cortisol and Cortisone are also provided, including the Cortisol Awakening Response.

What can the DUTCH Plus^® tell us that the DUTCH Complete™ cannot?

Even though a patient may have “normal” free cortisol levels throughout the day, that doesn’t always mean everything is functioning properly. The graph below shows two good examples. A blunted or exaggerated Cortisol Awakening Response (CAR) can appear, even when single samples return “normal” results. The HPA axis might not be appropriately responding when faced with a stressor, even when cortisol levels are fluctuating nicely throughout the day. The “stress” of waking allows us to test the HPA axis in a way that has been independently correlated to clinical outcomes and cannot be assessed by other cortisol tests on the market.

Why aren’t true Cortisol Awakening Response tests readily available?

A true CAR assessment requires salivary samples to be collected at the moment of waking, and twice more, at 30 minutes after waking and 60 minutes after waking. These specifically timed collections are difficult and impractical with urine and traditional salivary options. The DUTCH Plus^® uses specialty, FDA-approved, and patented collection devices called Salivettes™. Salivette™ are specifically made for testing cortisol when timing needs to be precise and are used in nearly all of the published CAR studies. The small synthetic cotton swab can be quickly saturated with saliva, providing a very fast and simple collection. Unfortunately for labs using saliva to test reproductive hormones, they are not a viable option as the swabs cannot be used when testing progesterone. The DUTCH Plus^® offers the most accurate salivary cortisol sampling with Salivette™ collection and analysis using LC-MS/ MS. An unparalleled clinical tool is created when combining salivary cortisol with the extensive urine metabolites from DUTCH.