The 5 Biomarkers Every Midlife Woman Should Know — Dr. Florence Comite
Precision-medicine pioneer Dr. Florence Comite argues you don't need 9,000 biomarkers — you need five, read together with your health story and family history. Fasting glucose, fasting insulin, hemoglobin A1c, the cholesterol risk ratio and free testosterone tell a story about almost every person she has seen. The theme running through the whole conversation: normal lab ranges and optimal ranges are two very different things.
Overview
Dr. Vonda Wright hosts Dr. Florence Comite, who founded the first women's-only clinic at Yale in 1992 and has run her own precision medicine and healthy longevity center since 2005. Comite's central frustration is that biomarker panels are now sold on every street corner, but almost nobody knows how to prioritize what actually moves the needle.
Her answer is to start small and interpret deeply: five biomarkers — fasting glucose, fasting insulin, hemoglobin A1c, cholesterol risk ratio and free testosterone — plus a continuous glucose monitor, a full health story and family history. She calls this the N of 1 approach: as an identical twin, she learned early that even genetically identical people are not the same. Much of the conversation dissects the gap between normal and optimal, using her own data as an example — an A1c below five that hid an insulin drifting to 15 or 20.
She also makes the case that testosterone in women is chronically under-discussed, tied to bone, cognition, memory and body composition, and starting its 1–3% annual decline as early as the thirties. Both women describe flipping their own priority order and landing on sleep first, then nutrition, then exercise. The closing note is a hopeful one: epigenetics means the way genes are expressed can be influenced by how you live.
Key quotes
5Do not get 9,000 biomarkers tested.
Those five can tell a story about every single human being I've seen.
You shouldn't have any insulin around when you fasted all night.
We have more testosterone in our body than estrogen as women.
Sleep is the critical element, because you will eat poorly and you will not exercise.
Key ideas
9Connecting the dots beats collecting the data
Comite says the hardest and most valuable skill isn't ordering biomarkers, it's interpreting them against how a person sleeps, eats, trains and where they come from. Knowledge alone isn't enough; she calls the interpretive layer wisdom.
Family history as a richer signal than genetics
She once called family history the poor man's genetic test and has changed her mind. What runs in your family is what has already shown up, or has the potential to show up, in you.
The N of 1 principle
As an identical twin with different tastes, habits and patterns from her sister, Comite treats every person as a unique system. Your friend's pattern, and even your sister's, is not your pattern.
The five biomarkers
Sugar metabolism (fasting glucose, fasting insulin, hemoglobin A1c and the relationship between them), the cholesterol risk ratio, and free testosterone. She notes fasting insulin is rarely drawn in conventional care and that total testosterone tells you little because it is protein-bound.
Normal versus optimal
Population reference ranges come from studies of people who were never defined as healthy, so average is not a target. She cites TSH ranging tenfold within normal while free T3 and free T4 go untested.
Averages hide the pattern
Her own A1c stayed under five while her insulin climbed to 15 or 20, because highs and lows averaged out. A continuous glucose monitor showed the swings that a single lab value erased.
Fasting isn't for everyone
She has never believed in one-size-fits-all diets and says roughly a third of people do well with intermittent fasting, a third drop dangerously low, and a third see no change at all.
Meal sequencing as a lever
Starting a meal with protein, fat and fiber rounds out glucose absorption instead of spiking it, and evens out the insulin that follows. Wright has her dinner guests served bread after the entrée for exactly this reason.
Testosterone as more than a sex hormone
Comite frames testosterone as central to bone, cognition, memory and energy, declining 1–3% a year from the thirties. She links the loss, rather than estrogen, to the truncal weight change many women notice.
Practical takeaways
6- 1
Start with five, not five hundred 12:15
Ask about fasting glucose, fasting insulin, hemoglobin A1c, the cholesterol risk ratio and free testosterone before paying for a giant panel.
- 2
Write down the optimal targets she names 17:20
She describes optimal as A1c under five, fasting glucose in the 70s, fasting insulin under two, and a cholesterol risk ratio at or under two — as discussion points with your own clinician, not self-diagnosis.
- 3
Look at trends, not single snapshots 24:15
One value at one moment says little. Comite asks patients for a year, two years, even decades of prior results before drawing conclusions.
- 4
Wear a continuous glucose monitor for a stretch 27:00
A few weeks of data shows how your own body responds to food, training and stress — far more informative than one fasting number.
- 5
Sequence your plate 34:00
Protein, fat and fiber first; a handful of nuts or a piece of cheese before the carbohydrate portion smooths the glucose and insulin response.
- 6
Protect sleep before you protect the workout 45:30
Both doctors landed on sleep as the first priority, then nutrition, then exercise — skipping sleep to train early tends to backfire on appetite and performance.
Topics & chapters
16Why she started before longevity was a thing
Wright introduces Comite's work: the first women's-only clinic at Yale in 1992 and a precision medicine practice since 2005.
Biomarkers on every street corner
The market offers thousands of markers with no framework for prioritizing them. Comite explains what interpretation actually requires.
Hormones as master communicators
Estrogen and testosterone are discussed as neuroendocrine signals reaching almost every tissue, not merely sex hormones.
FSH, bone and the silos of medicine
Wright shares what she recently learned about FSH and bone health, and both discuss how poorly knowledge travels between specialties.
The five biomarkers, named
Sugar metabolism, cholesterol risk ratio and free testosterone — with the reasoning behind each choice.
Normal versus optimal
Why population averages are the wrong target, illustrated with thyroid testing.
The seven patterns of aging
Comite describes the framework from her book and why most people carry two or three patterns at once.
Her own numbers as a case study
A beautiful A1c hiding a rising insulin, and what continuous glucose data revealed about her daily swings.
Sugar isn't evil
Keeping glucose even rather than eliminating sweetness, and what the highs and lows actually signal about how you feel.
Fasting, thirds and individuality
Why intermittent fasting works well for some and poorly for others, and what that says about generic advice.
The thrifty gene and modern abundance
Genes that helped ancestors survive famine now operate in an era of constant availability.
Protein, fat and fiber first
A practical sequencing habit for evening out glucose and insulin, plus Wright's bread-at-the-end dinner trick.
Epigenetics as a hopeful message
You can't change your genes, but expression responds to how you live — the core idea behind Comite's book.
Testosterone in women
Bone, cognition, memory and energy; the effect of birth control on ovarian testosterone; and how under-discussed the topic remains.
Sleep first, then food, then movement
Both doctors describe flipping their priority order and why sleep debt undermines everything downstream.
Biological age tests and closing thoughts
Comite's take on epigenetic clocks and telomere tests: useful, emerging, and best read as trends.