The Door That Is Still Open

THE TESTOSTERONE CRISIS · BONUS ARTICLE

He is seventy-three years old. He spent his entire working life ranching in the Colorado mountains. He is retired now, though retired is the wrong word for what he and his wife are doing with their seventies. They ride motorcycles together — not the way retirees sometimes ride motorcycles, short loops on weekends, but in groups, across multiple states, to events like the Sturgis rally in South Dakota each summer. They lift weights. They are both physically active at a level that most Americans thirty years younger would find demanding.

He came to me in 2022, at the age of sixty-nine. His total testosterone was 520 nanograms per deciliter. His free testosterone was 11.3. His luteinizing hormone was 6.1. He had the full constellation of low-T symptoms — the fatigue, the declining libido, the erosion of physical performance that had become difficult to ignore despite his activity level. If a man this lean, this conditioned, this relentlessly used was walking into my clinic with a total testosterone of 520, something was suppressing what his biology was clearly still equipped to produce.

I started him on a generic medication that costs less than a tank of gas. Twenty-five milligrams a day. The standard starting protocol. I retested him eight weeks later.

His total testosterone had climbed to 1,160 ng/dL. His free testosterone was 22.5, against a male reference range that tops out at 13.0 — well above the upper limit of the standard range. His LH had risen from 6.1 to 15.4. Every downstream signal was firing. The axis was not failing. It had been suppressed, and when the suppression was removed, it responded like the axis of a man forty years younger.

Two years later, his total testosterone peaked at 1,400 ng/dL.

I want you to sit with that number for a moment. A seventy-three-year-old retired rancher in the Colorado mountains is producing 1,100 to 1,400 ng/dL of his own testosterone.

The average American man in his twenties today, according to the Lokeshwar NHANES analysis, is producing 451.

A man born in 1953 is producing two and a half times more of his own testosterone at seventy-three than the average American man born after 1995 is producing at his biological peak. If testosterone decline were primarily an aging phenomenon — as the testosterone replacement industry has implied for decades when marketing to middle-aged and older men — this would be impossible.

It is not impossible. It is standard, in the older rural men I treat.

The medication that did this is called clomiphene citrate. It has been on pharmacy shelves for sixty years. It costs thirty to sixty dollars a month. It is generic, off-patent, and unapproved by the FDA for use in men — although its off-label use in male hypogonadism is supported by approximately two hundred peer-reviewed studies, is endorsed by American Urological Association guidelines for appropriate patients, and has been the standard of care among reproductive urologists for two decades. Most American men have never heard of it. Most American physicians have never prescribed it. The reasons for that absence — the pharmaceutical economics, the specialty fragmentation, the cognitive association with female fertility — are the subject of another article.

This article is about something else. This article is about what clomiphene does in older men whose hormonal axes were built before the chemical era reached its peak. And about why I am the one telling you about these men, and not the one in their group.

Permit me to interrupt the case.

In April 2007, at the age of fifty-three, I had my first testosterone panel drawn. I had begun medical school at forty. Through my training and early career I had maintained high energy, good libido, strong workout recovery. By all outward signs — including my own subjective assessment of how I felt — I was a healthy middle-aged man. By April 2007, something had changed. My energy had fallen. My recovery had become sluggish. My libido had declined in a way that I recognized, from the medical literature I was reading as a practicing physician, as consistent with hormonal change. So I ordered the panel.

My total testosterone came back at 1,030 ng/dL. The reference range topped out at 950. By the standard interpretation, I was not merely normal — I was above the upper limit. Any physician scanning the result, including me, would have closed the chart.

But my percent free testosterone was 1.5, flagged low.

This is the number that should have told me something was wrong. It is also the number that I, like most physicians of my generation, had not been trained to take seriously in the presence of a reassuring total. Total testosterone is the inventory on the loading dock. Free testosterone is what actually made it into the building. In April of 2007, my inventory looked fine. My bioavailable hormone was telling a different story. I did not yet have the framework to read it.

I retested over the next eighteen months. Total testosterone fell from 1,030 to 819, then to 574, then 694. By October 2008, my percent free had collapsed to 1.08. And my luteinizing hormone — the upstream signal from the pituitary that tells the testes to produce — was 2.9.

LH of 2.9 is within the stated reference range. It is not flagged. It would not trigger any laboratory alert. But 2.9 in a man whose total testosterone has dropped from 1,030 to 694 is not normal. It is inappropriately normal. If my testes were failing at the primary level, my pituitary should have been driving LH upward — values of seven, eight, ten or higher — to compensate. Mine was quiet. And quiet is the signature of secondary hypogonadism: suppression from above, in the hypothalamic-pituitary signaling system, not failure below in the testes themselves.

The framework that explains why a hypothalamus would suppress a middle-aged man’s LH signal in 2008 — the framework that identifies estrogenic endocrine-disrupting chemicals binding hypothalamic estrogen receptors as the upstream suppressor, and clomiphene citrate as the molecular countermeasure — did not exist in synthesized form at the time. It does now. It did not then.

So I went to Cenegenics. They were competent and well-intentioned. Their assessment confirmed what my outside labs had shown, and they caught one thing no one else had: at fifty-three, weight-training for thirteen years, lean and conditioned, I had osteopenia. Three months of testosterone reversed it.

I have been on testosterone replacement therapy ever since.

Eighteen years. The exogenous testosterone that resolved my osteopenia and restored my function has, over those years, suppressed the axis I might otherwise have rescued with clomiphene. My pituitary has been quiet for almost two decades. My testes have diminished. The door I did not know was closing in 2008 is now closed.

I have considered, periodically, whether to attempt the transition. I have treated patients who have tried. The results have been almost uniformly poor. The one patient I can recall who succeeded was a retired Navy SEAL who endured six full months with his natural testosterone below 100 ng/dL before his hypothalamus and pituitary finally responded to the clomiphene. He suffered greatly. That he persisted long enough to give his axis time to recover is, in my clinical experience, exceptional. At seventy-one, I have made the decision not to attempt it.

I am telling you this story for one reason. Because the decision I made in 2008 — a decision that seemed reasonable at the time, that was made with the best information I had access to, that was recommended by a competent and well-intentioned clinical program — is a decision that older American men are being offered, every day, by physicians who do not yet have the framework I am attempting to provide.

The men in the next section did not make that decision. Their doors are still open.

Peter W. is an engineer. He was sixty years old when he found me, and the way he found me is part of the story.

A few years before our first visit, I had written a short article about endocrine-disrupting chemicals, plastic water bottles, and clomiphene. Peter’s chiropractor had printed it out and kept it in his office. Peter read it while waiting for an adjustment. He went home and did his own research on clomiphene and enclomiphene — the kind of research a careful engineer does when he encounters a hypothesis that might explain a problem he has been trying to solve. Then he emailed me to request an appointment. The framework this article is describing has been circulating in printout form in chiropractors’ offices before it appeared in any medical journal. The people most motivated to find it have been finding it. The medical establishment has been the last to look.

Peter came in with the symptom pattern I had seen many times. Low energy. Low libido. Erectile dysfunction worsening over two years. He had tried testosterone pellets — they had not resolved his symptoms and had produced significant testicular shrinkage. He had tried topical AndroGel with poor results. He was, when he arrived, an educated patient who had tried the standard TRT options, watched them fail, and come looking for something different.

His initial labs were dramatic. Total testosterone 166 ng/dL. Free testosterone 3.3 picograms per milliliter, against a male reference range of 6.6 to 18.1. The Labcorp female reference range for free testosterone tops out at 4.2.

A sixty-year-old man who had been lifting weights consistently was walking into my clinic with bioavailable testosterone below the upper bound of normal for a woman.

I started him on clomiphene citrate. Four weeks later his total testosterone was 611. His free testosterone was 16.3, inside the normal male range for the first time in who knows how long. His LH had risen from 4.2 to 8.8.

That was eight years ago. Today, at sixty-eight, Peter remains on clomiphene. His most recent total testosterone is 575. His free testosterone is 19.8. His LH is 16. He has required no dose escalation. He has experienced no side effects. His energy and libido are restored. He works out regularly and has continued to do so for the full eight years of treatment. One honest caveat, because the credibility of everything else depends on it: his erectile dysfunction improved with the restoration of his testosterone but has not fully resolved. In my clinical judgment, this reflects vascular disease — plaque in the arteries that feed the cavernous tissue — that testosterone alone cannot reverse. He uses Viagra and Cialis with good effect. Clomiphene restored his axis. It did not restore the condition of vessels that decades of American middle-aged life had produced. The vascular plaque is a separate pathology requiring a separate therapy, and a physician who tells you otherwise is selling you something.

Eight years. Durable response. Axis preserved. His own testosterone.

Matt G. is sixty-eight. He came to me having tried testosterone pellets and testosterone troches with his previous physician, neither of which had given him sustained relief. His body had rejected the pellets. The troche dosing had been difficult to maintain. His initial labs in my clinic: total testosterone 661, free testosterone 81, LH 3.2.

I want you to notice his starting total. Six hundred sixty-one. By conventional reference-range standards, Matt was not even hypogonadal. But his symptoms told a different story, and his LH of 3.2 in the presence of those symptoms was the inappropriately-normal signal that I have been describing throughout this series. His axis was being suppressed. The standard reference range was hiding it.

I started him on clomiphene. Eight weeks later, his total testosterone was 1,014. His free testosterone was 211.9. His LH had risen from 3.2 to 7.7. He has continued on clomiphene. His total testosterone has reached as high as 1,253. He continues to respond. He continues to do well.

After he read one of my early articles on this topic, Matt posted a comment. He did so unsolicited. I had not asked him for a testimonial. He wrote what he wrote because the article had articulated something he had personally experienced, and he wanted other men to know. I reproduce his comment with his permission:

“I’ve been working with Dr Walters for nearly a year now. I had gone to see him as my previous efforts to increase my Testosterone (pellets, troche) had largely been unsustainable. I’m 68 years old and am at the age where men start to have concerns about their libido and sexual performance.”

“Introducing additional testosterone into my body, the approach favored by my previous medical provider, did push the numbers up but my body rejected the pellets and the troche I had trouble being consistent with.”

“Dr Walters method uses a different approach. By taking one clomiphene tablet daily my body is creating its own testosterone. My numbers were around 450 ng/dL then 661, and have increased to around 1,100.”

“What was astonishing was Dr Walters telling me my 450 number was probably double what a lot of young men in their twenties and thirties have these days.”

“Read his articles and see for yourself. It’s another sad, sad story on how our environment is destroying our civilization.”

I have spent twenty-five years as a physician writing about hormones. I have never written a sentence that captures the argument of my work more efficiently than the last sentence Matt wrote in the comment section of my Substack.

Three men. One started at a total testosterone of 520 and climbed to 1,400. One started at 166 — bioavailable testosterone below the female upper limit — and has held a restored axis for eight years. One started at a number his previous doctor would have called normal and reached 1,253. The longest course of treatment in my older-men practice is now eleven years. I have occasionally needed to escalate from 25 milligrams every other day to 25 milligrams daily, or to 50 milligrams every other day. I have never needed to exceed 50. No serious adverse events. No loss of response in the substantial majority.

Their axes were never told a lie loud enough or long enough to damage them permanently. When I removed the lie with clomiphene, the axes responded.

If you are a man in your fifties or sixties, and you are being evaluated for low testosterone, and your LH is low or inappropriately normal — meaning low, mid-range, or anywhere short of robustly elevated — the intervention you should be considering first is clomiphene citrate.

Not testosterone replacement therapy.

Not because TRT is wrong for everyone. For some men, particularly those with primary testicular failure or specific clinical situations, exogenous testosterone is the appropriate choice. But for the secondary-hypogonadism pattern that characterizes most American men in the current chemical environment, the choice between TRT and clomiphene is not symmetric. TRT works by overriding your axis. Clomiphene works by restoring it. TRT, started in your fifties, is a commitment that suppresses your endogenous production for as long as you remain on it — and as my own case demonstrates, the door becomes increasingly difficult to reopen the longer it has been closed. Clomiphene is reversible. If it does not work for you, you stop, and your physiology returns to baseline within weeks. The asymmetry of risk between these two interventions, properly understood, favors clomiphene as the first-line option for the patient population I am describing.

When you find a physician to discuss this with, the questions worth asking are these. Do you treat male hypogonadism with clomiphene citrate? Do you order a complete hormonal workup including LH, FSH, free testosterone, and estradiol — not just total testosterone? How do you think about endocrine-disrupting chemical exposure as a contributor to male hypogonadism? The answers will tell you whether the clinician is operating within the framework I have been describing or within the conventional TRT framework. For the patient population I have spent twenty-five years documenting, the framework I am describing is more likely to produce appropriate care.

If the clinician’s answers do not match the framework, you have options. The American Urological Association directory and the Society for the Study of Male Reproduction directory both list physicians with specific interest in male reproductive endocrinology. Telehealth options have expanded access to clinicians with this expertise. Patient persistence is sometimes required.

A brief honest scope-note before I close. Clomiphene is not for every patient. Men with primary testicular failure — identified by the laboratory pattern of low testosterone with elevated LH and FSH — do not respond to it. Men with significant thrombotic histories or certain liver conditions need a different approach. The selection of appropriate patients is part of the clinical art of male hormonal medicine. But for the secondary-hypogonadism pattern that characterizes the men I am writing about in this article — and that almost certainly characterizes a substantial portion of the readers of this Substack — clomiphene is the answer that the medical establishment has not yet learned to offer.

The rancher rode to Sturgis this summer with his wife. At seventy-three, he is producing more of his own testosterone than most men reading this article ever will, on a pill that costs less than dinner. Peter is eight years into clomiphene treatment, working out, functional, his own axis intact. Matt is producing testosterone at a level his previous physicians could not produce in his body with pellets, troches, or any of the exogenous interventions they tried — and he has used the comment section of this Substack to tell other men what is possible.

Their axes were never told a lie loud enough or long enough to damage them permanently. The chemical environment that has collapsed the testosterone of their grandsons reached them later in life, after their hormonal architecture had already been built. Their hypothalami remember how to work. The drug I prescribe them does nothing except remove the lie from the receptor. The axis does the rest.

My door has closed. I made my decision in 2008, in the absence of a framework that did not yet exist. I will remain on testosterone replacement for the rest of my life, and I have made my peace with that. I am writing this article because the decision I made is still being offered, every day, to men whose doors are still open.

If you are one of those men, you have a window. The biology is more durable than the medical system has given it credit for. The medication exists. The cost is trivial. The evidence base spans sixty years.

The question is whether you find a physician who knows.

* * *

Dr. David Walters is a physician with clinical and research training in men’s hormonal health. Nothing here constitutes medical advice or establishes a physician-patient relationship.

A bonus article from The Testosterone Crisis — that concluded last week. Watch for future articles where I provide information on how EDCs are impacting women’s testosterone levels as well.

Lokeshwar SD, et al. (2021). “Decline in Serum Testosterone Levels Among Adolescent and Young Adult Men in the USA.” European Urology Focus. https://pmc.ncbi.nlm.nih.gov/articles/PMC12299029/

Krzastek SC, et al. (2019). “Long-term safety and efficacy of clomiphene citrate for the treatment of hypogonadism.” Journal of Urology, 202(5), 1029–1035. https://pubmed.ncbi.nlm.nih.gov/31144610/

Whitten SJ, et al. (2006). “Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate.” Fertility and Sterility, 86(6), 1664–1668. https://pubmed.ncbi.nlm.nih.gov/17007840/

Katz DJ, et al. (2012). “Outcomes of clomiphene citrate treatment in young hypogonadal men.” BJU International, 110(4), 573–578. https://pubmed.ncbi.nlm.nih.gov/22243806/

Hayden RP, et al. (2020). “Clomiphene citrate in the management of male infertility.” Current Opinion in Urology, 30(3), 396–401. https://pubmed.ncbi.nlm.nih.gov/32132356/

Wheeler KM, et al. (2019). “A review of the efficacy and safety of clomiphene citrate for the treatment of male infertility.” Translational Andrology and Urology. https://pubmed.ncbi.nlm.nih.gov/30050802/

Soares AH, et al. (2018). “Clomiphene citrate as an alternative for testosterone replacement therapy: efficacy and safety.” Fertility and Sterility. https://pubmed.ncbi.nlm.nih.gov/29885893/