Ep. 38: The Critical Window for Hormonal Therapy to Prevent Heart Disease—Are You Missing It? — with Dr. Amy Killen, MD

For two decades, a single 2002 study scared a generation of women — and their doctors — away from hormones. In this episode, Dr. Regina Druz sits down with longevity and hormone-optimization physician Dr. Amy Killen to separate that history from what the science actually supports today. They unpack the ‘critical window’ (or timing hypothesis) for starting hormone therapy, why route and formulation matter (transdermal estradiol and bioidentical progesterone versus older oral, synthetic regimens), and what hormones do — and don’t — do for blood pressure, arterial stiffness, lipids, and inflammation across the menopausal transition. They also dig into testosterone safety in both men and women, progesterone’s underappreciated role, and how women can find trustworthy guidance. Throughout, both physicians stress that hormone decisions are deeply individual — this is education, not a prescription.

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Episode Chapters

[00:00] Introduction: Meeting in the Longevity Docs Community
[02:00] From the ER to Hormone Medicine
[05:22] “Thinking That Is Malpractice”: How the Field Shifted
[07:10] Hormones & the Heart: What the Data Shows
[08:22] The Women’s Health Initiative & the Black Box, Revisited
[12:01] Route & Timing: Transdermal, Bioidentical & the ‘Sweet Spot’
[15:23] The ‘Should’ vs. ‘Shouldn’t’ Box
[17:43] Perimenopause, Blood Pressure & Arterial Stiffness
[22:56] Targets, Levels & Symptom-Based Dosing
[26:24] Testosterone & Cardiovascular Safety in Men
[31:11] Progesterone’s Role & Testosterone in Women
[38:01] Where to Learn & a Message on Women’s Vascular Risk

Transcript

[00:00] Introduction: Meeting in the Longevity Docs Community

Dr. Regina Druz (00:02): Welcome to Own Your Heart Health. I’m Dr. Regina Druz, your holistic cardiologist. This week we’ll dive into common heart health concerns, uncovering root causes and unpacking scientific discoveries and controversies. The information provided does not constitute medical advice. Please contact your healthcare practitioner before making any changes that may impact your health.

Dr. Regina Druz (00:40): Hi everyone. I’m delighted to introduce a special guest, Dr. Amy Killen. Amy and I met in a wonderful physician community called Longevity Docs — there’s a terrific ladies’ group within it, organized in part by Dr. Poonam Desai, where women longevity physicians connect and learn from each other. Amy is a board-certified emergency physician who became a leading voice in hormone optimization, regenerative medicine, and women’s longevity. She’s the co-founder and Chief Medical Officer of Humanaut Health, the founder of the Human Optimization Project, and she teaches clinicians through a program she calls HOT — hormone optimization therapy. Amy, welcome.

Dr. Amy Killen (01:44): Thank you so much for having me — I’m thrilled to be here and to talk about one of my very favorite topics.

[02:00] From the ER to Hormone Medicine

Dr. Regina Druz (02:00): I ask all my guests: how did you grow up to become the doctor you are today? You started in emergency medicine, which is quite a different world.

Dr. Amy Killen (02:14): It is. I grew up in Texas and trained as an emergency physician — I practiced ER medicine for about ten years. I loved parts of it, but I had three kids in two years while working overnight shifts, and I hit a wall. I was burned out, and I started to feel like in the ER I was mostly putting band-aids on problems that had been building for decades. So in 2013 I left, moved to Portland, and opened a small clinic on my own, focused on hormones and what we’d now call longevity medicine. I knew almost nothing about running a business; I just knew I wanted to help people stay well instead of catching them after the crash. I later moved to Utah and grew what became one of the largest hormone-replacement practices in the state.

Dr. Regina Druz (03:48): That resonates with me. I came from traditional cardiology, and I had my own wake-up call that pushed me toward integrative and longevity medicine. There’s something about hitting that wall — realizing the system is built to react, not to prevent — that changes how you practice. And hormones sit right at the center of prevention for women, even though they’ve been treated almost as taboo.

[05:22] “Thinking That Is Malpractice”: How the Field Shifted

Dr. Regina Druz (05:22): Let me tell you a quick story. A few years ago I was at a major cardiology conference, and in the faculty lounge I overheard senior colleagues talking about hormone therapy as though prescribing it were practically malpractice — that’s how strong the fear still was. Fast-forward to today, and hormone optimization is discussed on main stages at longevity and even mainstream medical meetings. How do you reconcile that whiplash — from ‘never touch it’ to ‘everyone’s talking about it’?

Dr. Amy Killen (06:13): It’s a huge shift, and honestly a needed correction. For twenty years, fear from one study basically froze the field, and an entire generation of clinicians was trained to say no automatically. What’s happening now is that we’re re-reading the actual data — including reanalyses of that very study — and realizing the story is far more nuanced. Hormones aren’t a magic bullet and they aren’t poison; they’re a powerful tool that has to be used thoughtfully, in the right person, at the right time, in the right form.

[07:10] Hormones & the Heart: What the Data Shows

Dr. Regina Druz (07:10): So let’s get specific for our heart-focused audience. What do we actually know about estrogen and the cardiovascular system?

Dr. Amy Killen (07:22): The clearest signal is around timing. When estrogen therapy is started early — generally within about six years of menopause, or before age 60 — it appears safe for the heart and very likely reduces cardiovascular risk. Estrogen supports the endothelium, the lining of the blood vessels; it promotes nitric oxide and vasodilation, has favorable effects on lipids, and is anti-inflammatory. The open questions are about the details: the form of estrogen, the dose, the route, and — most importantly — the window in which you start. Oral and transdermal estrogen are not the same, and lumping them together is part of why older data looked scarier than it should have.

[08:22] The Women’s Health Initiative & the Black Box, Revisited

Dr. Regina Druz (08:22): This is the crux, isn’t it? The study that scared everyone was the Women’s Health Initiative in 2002. Walk us through what it actually used and found.

Dr. Amy Killen (09:18): The Women’s Health Initiative tested a specific combination: conjugated equine estrogen — Premarin, derived from horse urine — plus a synthetic progestin, medroxyprogesterone. Two things matter. First, the increase in breast cancer risk that grabbed headlines was driven largely by the synthetic progestin, not by estrogen itself. Second, the average participant was many years past menopause — often more than a decade — and that’s the group where starting hormones raised heart-attack risk. In the women who were closer to menopause when they started, the heart signal didn’t look the same; if anything, early starters tended to do well. So the trial mostly told us that a particular oral, synthetic regimen, started late, is the wrong approach — not that all hormones are dangerous.

Dr. Regina Druz (11:06): And that black-box warning shaped two decades of practice. It’s now being removed, or reconsidered. From your standpoint, was that warning justified — and is removing it justified?

Dr. Amy Killen (11:24): The warning made some sense for that specific regimen in that specific population, but applying it to every hormone, every route, and every woman was a massive overcorrection. Removing or softening it reflects what the data actually support — as long as we’re precise about who, when, and how. The danger now is the opposite overcorrection: treating hormones as risk-free for everyone. They’re not. It always comes back to the individual.

[12:01] Route & Timing: Transdermal, Bioidentical & the ‘Sweet Spot’

Dr. Regina Druz (12:01): So in your practice, what does a heart-conscious regimen tend to look like?

Dr. Amy Killen (12:10): For most women, the safest profile is transdermal estradiol — a patch, gel, or cream — paired with bioidentical (micronized) progesterone, rather than older oral synthetic combinations. Transdermal estrogen largely avoids the clotting risk associated with the first-pass liver effect of oral estrogen, which matters a lot for vascular safety. And the ‘sweet spot’ is timing: ideally starting within that roughly ten-year window after menopause and before age 60, and being far more cautious about initiating hormones in someone who is well past that window or who already has established cardiovascular disease.

Dr. Regina Druz (13:25): That’s a key point for cardiologists — route and timing aren’t details, they’re the whole ballgame. And I’d add my usual framing: population data gives us the floor. Even within that window, I want to know the individual’s vascular status — do they have plaque on imaging, what’s their arterial age — because that personalizes the risk-benefit conversation rather than relying on averages.

[15:23] The ‘Should’ vs. ‘Shouldn’t’ Box

Dr. Regina Druz (15:23): Let’s make it practical. How do you decide who should be considering hormones and who shouldn’t?

Dr. Amy Killen (15:36): I think of it as two boxes. Broadly, I’m a fan of hormone therapy for most women going through the menopausal transition, unless there’s a clear reason not to — the ‘shouldn’t’ box. That box includes things like a current or recent hormone-sensitive cancer, a history of certain clots or strokes, or other specific contraindications, where the decision has to be individualized and often shared with oncology or other specialists. Outside that box, the ‘should consider’ reasons are long, because estrogen touches metabolism, the mitochondria, the immune system, inflammation, bone, brain, and blood vessels.

Dr. Amy Killen (17:16): If I had to name the top reasons in the ‘should consider’ box from a cardiometabolic view, they’d be: dampening the rise in inflammation and immune dysregulation that comes with estrogen loss; the favorable effects on lipids — especially relevant because oral estrogen affects lipids differently than transdermal; and the mitochondrial and metabolic support, since so much of midlife cardiovascular risk in women is really metabolic.

[17:43] Perimenopause, Blood Pressure & Arterial Stiffness

Dr. Regina Druz (17:43): That cardiometabolic angle is exactly where I live. So much of the dyslipidemia I see in midlife women is actually driven by emerging insulin resistance, not a primary cholesterol problem. Let’s talk about perimenopause specifically — I define it loosely as the decade or so before menopause, often starting in the early 40s, when hormones become erratic. I see labile, up-and-down blood pressure in that window, and roughly a quarter of women develop early hypertension. What’s your read on hormones and blood pressure?

Dr. Amy Killen (19:44): The blood-pressure data is honestly weaker and messier than the lipid or inflammation data, so I’m careful not to overstate it. Mechanistically, estradiol promotes nitric oxide and vasodilation, which should help — and many women feel their vascular symptoms calm down. But blood pressure is multifactorial, and I wouldn’t prescribe estrogen as a blood-pressure drug. I’d say it can be supportive in the right person, not a treatment for hypertension on its own.

Dr. Regina Druz (20:25): That’s fair. What I find striking is the link between vasomotor symptoms — hot flashes and night sweats — and vascular health: women with more severe vasomotor symptoms seem to carry a higher burden of hypertension and measurable arterial changes. In my practice I look at arterial stiffness directly, with pulse wave velocity and vascular-age staging, because it gives an objective read on how the vessels are doing rather than relying on symptoms alone. It turns ‘how do you feel’ into ‘here’s what your arteries are actually doing.’

[22:56] Targets, Levels & Symptom-Based Dosing

Dr. Regina Druz (22:56): Here’s a debate I’d love your take on. The major menopause organizations generally say: treat symptoms, don’t chase hormone levels. But many optimization-minded clinicians do check and target levels. Where do you land?

Dr. Amy Killen (23:20): I do check levels — thoughtfully. The official guidance to treat symptoms rather than numbers exists partly to keep things simple and safe at the population level, and partly because symptom relief is the primary goal. But levels give me useful information, especially for things beyond hot flashes — bone protection, for instance, may need a certain estradiol level. In my own practice I often look for an estradiol somewhere in the range of about 65 to 150 picograms per milliliter, with something around 100 frequently enough to relieve vasomotor symptoms — but I want to be clear that those are my clinical reference points, individualized per patient, not universal targets. I pair that with the whole picture: symptoms, other labs, and the person’s goals. For men on testosterone, similarly, I’m generally aiming for the mid-to-upper end of the normal reference range rather than supraphysiologic levels.

[26:24] Testosterone & Cardiovascular Safety in Men

Dr. Regina Druz (26:24): Let’s go there, because testosterone has its own scary history. For years there was a black-box-type concern about testosterone and the heart in men. Where does that stand?

Dr. Amy Killen (27:03): It’s improved a lot. Around 2013 and 2014 there were a couple of widely publicized studies suggesting cardiovascular harm from testosterone — one of them even included women — and they drove a lot of fear and a warning. But they had real methodological problems. More recently, a large, better-designed trial looked specifically at cardiovascular safety, and broadly speaking it was reassuring — honestly, neither of us is going to remember the name on the spot — to the point that the older blood-clot-and-heart black box has largely been removed, leaving mainly a caution around blood pressure.

Dr. Amy Killen (28:33): The main mechanisms I actually watch for are erythrocytosis — testosterone can raise the red-blood-cell count and thicken the blood, which in excess could raise cardiovascular risk through hyperviscosity — and effects on blood pressure and fluid. So I monitor hematocrit and blood pressure. I’m more cautious in a man who already has poorly controlled hypertension or untreated sleep apnea, because testosterone can aggravate both. Used carefully and monitored, though, testosterone in men is much safer than its reputation suggested, and there’s a strong argument that low testosterone itself is associated with worse metabolic and cardiovascular outcomes.

Dr. Regina Druz (29:43): That tracks with what I see — low testosterone often travels with insulin resistance, visceral fat, and the whole metabolic picture that drives cardiovascular aging. So it’s not just about the hormone in isolation; it’s about the metabolic terrain it sits in.

[31:11] Progesterone’s Role & Testosterone in Women

Dr. Regina Druz (31:11): Progesterone doesn’t get nearly enough airtime. What should people understand about it?

Dr. Amy Killen (31:24): I call progesterone the yin to estrogen’s yang — the project manager that balances estrogen, protects the uterine lining, and does a lot more. Bioidentical progesterone is metabolized into allopregnanolone, which acts on GABA receptors in the brain, so for many women it’s calming and sleep-promoting. But responses vary enormously, and I think about three groups: women who tolerate it beautifully and feel calmer and sleep better; women who have a paradoxical response — they feel anxious, agitated, or wired instead of calm; and a small group, maybe around one percent, who have a true progesterone allergy or hypersensitivity. Knowing which group a woman is in changes how I dose, what form I use, and whether I adjust timing.

Dr. Regina Druz (33:47): That paradoxical response is so important clinically — I’ve seen women told they ‘can’t tolerate hormones’ when really the issue was the form or the timing of progesterone, not hormones as a whole. And there are downstream effects on the stress axis and sometimes on blood pressure worth watching. What about testosterone in women?

Dr. Amy Killen (35:00): I’m a fan of testosterone for many women, though not every woman needs it. Women make testosterone too — from the ovaries and adrenal glands — and it continues to matter after menopause. Officially, the only evidence-based indication recognized by the major societies is hypoactive sexual desire disorder — low libido causing distress — but clinically many women report benefits for energy, mood, muscle, and overall vitality. I individualize it, keep doses physiologic, and monitor. As with men, I’m watching the whole metabolic picture, not just one number.

Dr. Regina Druz (36:15): And from the cardiometabolic side, testosterone supports muscle, and muscle is one of our best defenses against insulin resistance — which loops right back to heart health. So in women, I see the libido benefit as real but almost the tip of the iceberg; the body-composition and metabolic effects may matter just as much for long-term cardiovascular risk.

[38:01] Where to Learn & a Message on Women’s Vascular Risk

Dr. Regina Druz (38:01): This field is moving fast, and patients are confused. Where should women turn for trustworthy information — because a lot of what’s online, and what AI tools say, is outdated or wrong?

Dr. Amy Killen (38:18): You’re right that AI often gets this wrong — it tends to parrot the old, fear-based framing from twenty years ago. My advice: look for clinicians and educators who actually keep up with the current literature, talk to friends who’ve had good experiences, and lean on credible organizations. The Menopause Society — formerly the North American Menopause Society — is a solid starting point for both patients and clinicians. I also write about this on my Substack in plain language, and I teach clinicians through my HOT course so more doctors can offer this competently.

Dr. Regina Druz (39:38): I’ll second the Menopause Society, and I’ll point listeners to your Substack, because the public deserves clear, current information. For the clinicians listening, Amy’s HOT — hormone optimization therapy — program is a way to actually learn to do this well, which we badly need. Any closing thoughts?

Dr. Amy Killen (40:12): Patients are getting more sophisticated, and that’s wonderful — they come in informed and ready to partner. I’m also writing a book on women’s longevity through the lens of reproductive and ovarian aging, due out in early 2027, because I think that lens reframes how we approach midlife health. Mostly I want women to know they have options, and that they don’t have to white-knuckle their way through this transition.

Dr. Regina Druz (40:59): That’s the message I want to leave our listeners with too. Roughly ten times as many women die of cardiovascular disease as of breast cancer, yet women are far more frightened of breast cancer — and far less likely to be screened for, or counseled about, their heart and vascular risk. So please, take your heart as seriously as you take your mammogram: ask about your blood pressure, your lipids, your arterial age, and whether hormone therapy belongs in your individual plan. Amy, thank you so much — this was fantastic.

Dr. Amy Killen (43:14): Thank you for having me — this was a joy.

Dr. Regina Druz (43:17): Thank you for tuning in to Own Your Heart Health with Dr. Regina Druz. This podcast is powered by Holistic Heart Centers. If you enjoyed the show, please rate and review us on your favorite platform. To learn more about our services, visit holisticheartcenters.com and subscribe to our YouTube channel — the link is in the show notes. See you next week.

Frequently Asked Questions

Is hormone replacement therapy safe for the heart?

According to Dr. Killen, the key factor is timing. When estrogen therapy is started early — generally within about six years of menopause, or before age 60 — it appears safe for the cardiovascular system and very likely reduces risk, because estrogen supports the blood-vessel lining, promotes nitric oxide and vasodilation, favorably affects lipids, and is anti-inflammatory. Route and form also matter: transdermal estradiol (patch, gel, or cream) with bioidentical progesterone has a more favorable vascular-safety profile than the older oral, synthetic regimens. Both physicians stress that hormones are neither a magic bullet nor poison, that women with certain conditions (such as a hormone-sensitive cancer or specific clotting history) may be advised against them, and that every decision must be individualized with your own clinician. This is educational information, not medical advice.

What was the Women’s Health Initiative — and why did it scare everyone off hormones?

The Women’s Health Initiative (WHI), published in 2002, tested one specific combination: conjugated equine estrogen (Premarin) plus a synthetic progestin (medroxyprogesterone). Dr. Killen explains two crucial points often lost in the headlines. First, the increase in breast cancer risk was driven largely by the synthetic progestin, not by estrogen itself. Second, the average participant was many years past menopause — often more than a decade — and that late-starting group was where heart-attack risk rose; women closer to menopause when they started generally fared better. The takeaway, she argues, is that a particular oral, synthetic regimen started late is the wrong approach — not that all hormones are dangerous. The resulting black-box warning shaped two decades of overly cautious practice and is now being reconsidered.

What is the ‘critical window’ for starting hormone therapy?

The ‘critical window’ (also called the timing hypothesis) is the idea that the cardiovascular effect of hormone therapy depends heavily on when it’s started. Started early — roughly within ten years of menopause and before age 60 — estrogen appears safe and likely heart-protective. Started well outside that window, especially in women who already have established cardiovascular disease, the risk-benefit balance shifts and caution is warranted. Dr. Druz adds that even within the window she likes to personalize the decision using the individual’s vascular status — for example, whether imaging shows plaque, and what the person’s arterial age is — rather than relying on population averages alone. Decisions about timing and candidacy should always be made with a qualified clinician.

Is testosterone therapy safe for the heart, in men and women?

Dr. Killen notes that testosterone’s cardiovascular reputation has improved. Two widely publicized studies around 2013–2014 suggested harm and drove a warning, but had methodological problems; a more recent, better-designed trial focused on cardiovascular safety was broadly reassuring, and the older clot-and-heart black box has largely been removed (leaving mainly a blood-pressure caution). The main things she monitors in men are erythrocytosis (testosterone raising the red-cell count and blood thickness) and blood pressure, with extra caution in poorly controlled hypertension or untreated sleep apnea. In women, the only societally recognized indication is hypoactive sexual desire disorder, though many report broader benefits; she keeps doses physiologic and monitors. (Both physicians note a recent landmark testosterone-safety trial whose name they couldn’t recall on air — see the show notes.) Always individualize with your clinician.

Show Notes & Resources

Guest: Dr. Amy Killen, MD

Dr. Amy Killen is a board-certified emergency physician who became a leading voice in hormone optimization, regenerative medicine, and women’s longevity. She is the co-founder and Chief Medical Officer of Humanaut Health (a longevity clinic franchise with locations in Utah and Texas) and the founder of the Human Optimization Project (HOP / HOPBox.life), a female-focused supplement company. She earned her MD at the University of Texas Southwestern and completed emergency-medicine training at the University of Arizona, and has spent more than a decade in longevity medicine, prescribing bioidentical hormones for 13+ years. An international speaker, educator (including her HOT — Hormone Optimization Therapy — course for clinicians), and soon-to-be author, she lives in Salt Lake City. (Disclosure: Dr. Killen has commercial interests in a clinic franchise, a supplement company, and a clinician training course.)

Dr. Amy Killen on Substack — plain-language education on hormones & longevity
Humanaut Health — longevity clinic franchise (humanauthealth.com; verify URL)
Human Optimization Project (HOP) — HOPBox.life (female-focused supplements)
HOT — Hormone Optimization Therapy — her training course for clinicians

Resources Mentioned in This Episode

The Menopause Society (formerly the North American Menopause Society) — credible patient and clinician information on menopause and hormone therapy
Dr. Amy Killen — Substack (dramybkillen.substack.com), Humanaut Health, the Human Optimization Project (HOP/HOPBox.life), and her HOT clinician course; women’s-longevity book due early 2027
The Women’s Health Initiative (2002) — historical context for the hormone black-box warning now being reconsidered (used conjugated equine estrogen + synthetic progestin)
Women’s vascular screening — blood pressure, a lipid panel, and measures of arterial stiffness / vascular age (e.g., pulse wave velocity), plus imaging such as a coronary calcium score where appropriate
Longevity Docs community & Dr. Poonam Desai — the physician community (and ladies’ group) where Dr. Druz and Dr. Killen connected
Recent testosterone cardiovascular-safety trial — referenced on-air but not named by either physician (likely the TRAVERSE trial, 2023 — please verify before citing)
Schedule a consult with Holistic Heart Centers — go.holisticheartcenters.com/apply

Holistic Heart Centers

holisticheartcenters.com
HeartWell.ai — AI-powered cardiovascular risk assessment
Address: 55 Bryant Avenue, Suite #6, Roslyn, NY 11576
Phone: 877-511-5166
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Instagram: @dr.reginadruz
Podcast: Own Your Heart Health — available on Apple Podcasts, Spotify, and all major platforms

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