Prolactin and Thyroid in Men: the overlooked axes

Perhaps you know this. The desire is gone, the drive flat, perhaps things in bed no longer work as reliably. At the doctor testosterone is measured, it is low, and the obvious explanation reads: too little testosterone, so top up testosterone. Sometimes that is right. Sometimes it is only half the story. Because testosterone is the last step of a long chain of command that begins in the brain.

In this chain of command there are two players who are rarely named first. Prolactin, which can brake the control from above. And the thyroid, which through a binding protein co-determines how much testosterone circulates in the blood at all and stays active. This spoke article is devoted to exactly these two axes. We look at the mechanisms, at real studies, and at when which values make sense.

Prolactin: the quiet brake in the male hormone system

Most people know prolactin as the breastfeeding hormone in women. That the male body produces it too surprises many. In small amounts this is entirely normal and part of the healthy hormone concert. It becomes interesting when prolactin is persistently too high. This state is called hyperprolactinemia, and in men it can set a whole chain in motion.

The decisive point is the control. High up in the brain, in the hypothalamus, the hormone GnRH is released in pulses. It is the timekeeper that, through the pituitary gland, instructs the testes to build testosterone. Elevated prolactin can disturb this rhythm. It brakes the GnRH pulses, the signaling hormones LH and FSH fall, and testosterone may follow. The result is a so-called secondary or central hypogonadism, that is a testosterone deficiency whose root does not lie in the testes but in the control center above them.

And now it becomes clear why the order of the workup matters so much. Whoever gives testosterone straight away for low testosterone and low signaling hormones may be treating the symptom and overlooking the cause up in the system. This is exactly why prolactin belongs on the lab list with this constellation of findings.

The prolactinoma: common, benign, often detected late in men

The most common cause of a marked hyperprolactinemia is a prolactinoma. This is a usually benign tumor of the pituitary gland that produces too much prolactin. It is the most common hormone-producing pituitary tumor of all. The word tumor sounds threatening at first, yet most prolactinomas are small and treatable.

In men there is a problem with time. Prolactinomas are often detected later in men than in women. In women a hyperprolactinemia draws attention early through cycle disturbances. In men it shows up as loss of libido, erectile problems, or fatigue, and these complaints are easily attributed to age, to stress, or to the job. So sometimes a lot of time passes before anyone thinks of prolactin.

One special case belongs here clearly, before we go on. Headaches and visual disturbances from a pituitary tumor usually develop slowly. But when a headache sets in suddenly and at its worst, and loss of vision, visual field defects, or double vision come with it, that is not a case for the next free appointment. Then it goes straight to the emergency department or through the emergency number, in Germany 112, because an acute bleed into the pituitary gland can be behind it. In such a case, hours decide how much vision is preserved.

How often something at the pituitary gland really lies behind unclear men's complaints has been investigated more closely by researchers. An analysis from the Cleveland Clinic gives a helpful orientation here.

The thyroid: through SHBG right inside the testosterone level

Let us come to the second overlooked axis. The thyroid is the timekeeper of metabolism. It determines how fast the cells work. That it also has a hand in the testosterone level is less well known, but well founded. The main route runs through a binding protein with the unwieldy name SHBG, sex hormone-binding globulin.

SHBG is something like a taxi for testosterone in the blood. Only the unbound, free testosterone is immediately active. How much SHBG is present therefore changes how the testosterone is distributed. And this is exactly where the thyroid steps in. In an overactive thyroid SHBG rises, so more testosterone is bound. Total testosterone can then look high, although the free, active testosterone does not rise accordingly. In an underactive thyroid SHBG tends to fall, and total testosterone can appear lower. Whoever looks only at the total value can easily be misled here.

An older but very clear review by A. Wayne Meikle from 2004 in the journal Thyroid frames the interplay further. A primary underactive thyroid can go along with a hypogonadotropic hypogonadism that can recede again under thyroid hormone replacement. In an underactive thyroid, prolactin can also rise and fall again after treatment. Men with an overactive thyroid have higher SHBG and testosterone values and more often a breast enlargement (doi:10.1089/105072504323024552, PMID: 15142373). And now you can see why the thyroid and prolactin belong together in this story. A pronounced underactive thyroid can set both axes in motion at once.

The four KPNI lenses on prolactin and the thyroid

In clinical psychoneuroimmunology, KPNI for short, we look not at a single hormone but at four interwoven levels. With prolactin and the thyroid this view is especially valuable, because both axes sit far up in the system and are influenced from several sides. Each lens explains one part at the cell level.

These four lenses are no theoretical model. They are the reason why a good workup for loss of libido and low testosterone does not stop at testosterone. And now you know why prolactin and the thyroid are so often the missing puzzle pieces.

Thyroid, erection, and mood: an underrated connection

The thyroid acts not only through lab values. It can also make itself felt directly in the sex life and in the mood. Both an overactive and an underactive thyroid are associated with sexual dysfunction in men. This is clinically relevant, because it means the thyroid belongs on the test bench for erectile problems.

That a treatment of the thyroid could change more than just lab values is shown by a small controlled investigation. Robert Krysiak and colleagues found in 2017 in the Pharmacological Reports a worse sexual function and more depressive symptoms in men with an autoimmune underactive thyroid than in healthy men. Under six months of treatment with the prescription-only thyroid hormone levothyroxine, erectile function improved in this small group, and in the pronounced underactive thyroid the depressive symptoms also decreased (doi:10.1016/j.pharep.2017.01.005, PMID: 28315587). This applied to men with a demonstrated underactive thyroid. A treatment without that proof is not sensible and can do harm, because too high a dose can promote cardiac arrhythmias and over time burden the bone. The groups were small, so restraint is appropriate. But the direction is plausible and fits the mechanism.

A broad review by Rohan Morenas and colleagues in 2023 in the International Journal of Impotence Research frames the field. It describes that thyroid disorders can contribute to sexual dysfunction in men through several routes, from erectile and ejaculatory disorders to a disturbed control of the testicular axis, and it argues for thinking of the thyroid in the workup (doi:10.1038/s41443-023-00768-4, PMID: 37752332). And now you know why the thyroid is more than a metabolic topic.

When which values? A sober orientation

This brings us to the practical question that occupies many men. When is it worth measuring prolactin and the thyroid alongside, and what matters there? Up front: this section does not replace a medical workup. It is meant to help you ask the right questions.

The most important hint is the constellation of findings. When a low testosterone occurs together with low or inappropriately normal signaling hormones LH and FSH, that points upward toward the brain. Exactly then prolactin and the thyroid are obvious next steps. A review by Shiri Levy and colleagues in 2019 in the Current Urology Reports stresses that with low gonadotropins, reversible causes in the hypothalamic-pituitary axis should be considered, and that men with a small prolactinoma stand out more with sexual complaints, while larger tumors tend to make problems through their size (doi:10.1007/s11934-019-0935-z, PMID: 31734886).

With a breast enlargement the look at both axes is especially worthwhile, because both a hyperprolactinemia and an overactive thyroid are among the possible causes. A review by Andrea Sansone and colleagues in 2016 in the journal Endocrine describes that a true gynecomastia often arises from an imbalance between estrogen and androgen and names hyperprolactinemia and an overactive thyroid explicitly among the hormone disorders to be evaluated (doi:10.1007/s12020-016-0975-9, PMID: 27145756).

A word on the breast before we go on: not every change in the male breast is hormonal. A one-sided, hard lump, a retracted nipple, a skin change over it, or a bloody discharge belong examined without delay, because men can develop breast cancer too, even if rarely. This is not scaremongering, it is the right order. First that is ruled out, then we look at prolactin, the thyroid, and the ratio of estrogen to testosterone.

With the prolactin measurement itself, care pays off at the blood draw. Stress, physical exertion, and some stimuli can briefly raise the value. A single slightly elevated value should therefore be checked calmly and ideally repeated before further steps follow. Two measurement traps belong here, because they can mislead in both directions. Part of the prolactin can be present as so-called macroprolactin, a form that is measured along in the lab but has little effect in the body. A high value without matching complaints can be checked specifically for this. And conversely, very high amounts of prolactin can produce a falsely low reading when the test is not repeated in dilution. Both are lab routine, as long as one thinks of them. The medication list belongs to this too, because some agents can raise prolactin without a tumor being behind it. A comprehensive review on pituitary insufficiency reminds us that in men a hypogonadotropic hypogonadism goes along with low testosterone and low or normal LH and FSH, and that hyperprolactinemia and a low SHBG belong in the differential diagnosis (doi:10.1007/s11102-006-0416-5, PMID: 17077946).

And there is an in-between situation. A small retrospective analysis of 23 men describes complaints such as loss of libido and erectile problems with elevated prolactin, although testosterone lay in the normal range (doi:10.1371/journal.pone.0332871, PMID: 40966237). That is a very small observation and carries no general rule. But it suggests that a normal testosterone does not automatically invalidate an elevated prolactin value.

Three levers you hold in your own hands

First the most important thing: a prolactinoma and a true thyroid disorder belong in specialist care. No lifestyle lever replaces a medical workup or a necessary therapy. These three levers are a start and a stance, not a treatment plan. You will find the individual path with medical guidance.

And when the complaints remain despite good foundations, a workup belongs to it that keeps the whole picture in view. Testosterone, LH, FSH, prolactin, and thyroid values together give a much clearer picture than a single value. This way treatable causes can be recognized sooner, rather than attributing complaints prematurely to one hormone. A careful workup looks at the whole picture and not at a single value.

Frequently asked questions about prolactin and the thyroid in men

Connections to other topics