Male Menopause: Fact or Fiction?

September 24th, 2010 § 13 comments § permalink

I hear that Mel Gibson allegedly blamed what he called depressed and “whacky” behavior on “male menopause.” Putting aside the question of whether he actually wrote the note circulating on the internet, (and that’s a big if,) is there a male menopause?  If the answer is yes, can it affect behavior and cause depression?

Testosterone levels do decrease, especially as a man gets older.  In one study, testosterone fell on average 110 ng/dL each decade in men over sixty.  As the FDA puts the normal line for testosterone in men at 300 ng/dL, that’s a big drop.  But it’s happening over ten years.

That’s the essential problem with calling the decline in testosterone as men age “menopause.” The word refers to the rapid plummet of women’s reproductive hormones around age fifty.  When a woman’s hormones drop in a short timespan, it’s fairly obvious to her that they’re changing .  But male hormones fall more gradually, though the decline is substantial.

Worse, a blood protein called “sex hormone binding globulin,” SHBG for short, is on the rise in the older man.  As its name implies, SHBG binds testosterone and renders it useless.  The drop in testosterone as men age is magnified by the climb in SHBG.

If testosterone was unnecessary, its decline would go unnoticed, but it’s one of the most important hormones a man has.  Low testosterone in older men is associated with muscle wasting, thinning of bones, loss of sex drive, depression and other problems.  Testosterone isn’t the only reason for these ailments, but it can be a big part of the puzzle.

If Mel did blame depression on “male menopause,” meaning a low testosterone, it’s possible that the 54 year old actor is feeling a drop in his hormones.  If he hasn’t already, he’ll want to get his testosterone checked.

The Penis as Barometer

July 21st, 2010 § 2 comments § permalink

You can’t fault a man for thinking his penis a single use tool.  But it’s more like a Leatherman or a good Swiss Army knife.  One great use is as a barometer for gauging the health of a man’s heart and blood vessels.

The structure of the penis is basically a sponge with a tiny artery that supplies blood.  The sponge fills with blood, and the penis becomes erect.  (It’s actually a really impressive piece of engineering, with veins at the outer edge of the sponge that are pressed closed as the penis fills, trapping the blood and holding the erection.)  The artery supplying the sponge is very small, only about half the diameter of the coronary blood vessels supplying the heart.  If the arteries are getting clogged, the arteries in the penis go before the heart ones do, giving a man a two to five years heads-up that something bad is happening, not just to the penis, but that may be life-threatening.

Recently published guidelines recommend that if a man is experiencing problems with erections, that he be evaluated for high cholesterol and other artery clogging problems, and that if the labs are out of whack, he be treated aggressively with medication.

As important as the penis is, the heart’s kind of necessary.

Doctor’s Corner: Clomiphene Rx

July 6th, 2010 § 88 comments § permalink

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Doctor’s Corner

Ever so often, I get asked questions from doctors, and I figure that here is a reasonable place to put how I answer the frequently asked ones.  As with everything I write, it’s my opinion, and doctors opinions vary.

One question I get asked a lot is how to prescribe clomiphene for a male.  Here’s how I do it.

First, clomiphene works by stimulating the pituitary.  If the pituitary’s already in overdrive, clomiphene won’t help.  So if a man’s LH is high, like 25 IU/L, I don’t prescribe clomiphene.

The next decision to make is what the target for therapy will be.  If it’s augmenting a low testosterone level, then I’ll use the bioavailable testosterone calculation described in a previous post.  As a reasonable threshold for total testosterone is 300 ng/dL and the portion of bioavailable testosterone ranges between 52% and 70%,1 I use the range between 156 ng/dL to 210 ng/dL as a lower limit of what is likely an adequate bioavailable testosterone level for a man.  If the target for clomiphene therapy is stimulating the testis to make sperm, I use a higher threshold.  If possible we try for twice as much, about 400 ng/dL for bioavailable and 600 ng/dl for total testosterone.  It’s not always possible to achieve those levels.

I start with 25 mg clomiphene a day.  As the pills come in 50 mg, and the half-life is relatively long, patients can take a pill every other day.  Some prefer talking half a 50 mg pill daily.  After two weeks, I have the patient get tests for testosterone, LH, albumin, SHBG (sex hormone binding globulin) and estradiol.  In some instances, the estradiol will increase, but as long as the ratio of total testosterone to estradiol is greater than ten-to-one, that shouldn’t be a problem.  If the estradiol increases substantially, other therapy, like an aromatase inhibitor, is preferred.  If the testosterone is still low, then we’ll increase the clomiphene by 25 mg every other day or daily, and repeat the tests.  I’ll increase the clomiphene to a maximum of 100 mg daily.

I believe that clomiphene works better if a man’s testosterone is low.  That’s a good indication that there is a problem that may be corrected.  If the testosterone is reasonable at the start, 400 ng/dL or more, then pushing it higher may not be as effective.  But that’s my opinion, and as of present, scientific studies don’t definitively prove it right or wrong.

It’s important to note that clomiphene is “off-label” for use in the male.  I explain this in a previous post.

1S. Bhasin. Chapter 18: Testicular disorders.  In: Kronenberg H. M., Melmed S., Polonsky K. S., and Reed Larsen P., eds. Williams Textbook of Endocrinology 11th ed. Philadelphia, W.B. Saunders Company, 2008; 647.

Varicose Veins in the Scrotum: What’s the Deal?

June 16th, 2010 § 124 comments § permalink

The testes must be kept cool for the proper production of sperm.  One way the human body achieves this is to house them outside the body.  Another is to have a network of veins surrounding the artery pumping blood into the testis: the veins take the heat away in a “counter-current” heat exchange similar to a radiator.  (The human body is an amazing piece of engineering.)

Arteries don’t need to worry about moving blood; there’s a huge amount of pressure coming from the heart to help with that.  But once the blood goes through the capillaries and into the veins, getting back to the heart isn’t easy.  Veins have little valves to help hold the blood while it pulses its way back.  If those little valves start to separate, the vein expands, causing the condition known as a “varicose vein.”  Varicose veins can happen in many places in the body, often visibly in the skin of the legs, but, believe it or not, also in the scrotum.  And if varicose veins develop in the scrotum, they can disturb the counter-current heat exchange.  The testes then get hot, posing a problem for developing sperm cells.

Varicose veins in the scrotum are called a “varicocele,” and there are three kinds.  A grade I varicocele can’t be felt or seen without equipment like ultrasound.  Almost all experts now consider grade I varicoceles to be unimportant.  Varicoceles that can be felt (grade II) or visible by the naked eye (grade III) are the ones that may cause problems with sperm production. Some men have such high sperm production that their varicoceles don’t significantly alter their chance of making women pregnant.  But many men’s testes are affected by grade II or III varicoceles.

Inside of a man, the left vein draining the testis back towards the heart is longer than the right. As a result, varicoceles are most often found in the left scrotum. Sometimes, they’re on both sides, and infrequently, they’re on the right side alone. A right sided varicocele that suddenly appears in adult life is worrisome, as it may be a sign of kidney cancer.

What can be done about a varicocele that may be throwing a wrench into the sperm factory?  A urologist can tie or clip the veins in a procedure called “varicocelectomy,” or an interventional radiologist can inject material into the veins to block the flow of blood.

The New WHO

June 9th, 2010 § 13 comments § permalink

A first test of male fertility is the semen analysis.  You do your thing, and a technician counts the sperm, sees how they’re moving, what they look like and whether they’re alive.  For decades, the World Health Organization has published criteria for these numbers to alert a man that he might have a problem when it comes to impregnating a woman.  Until recently, the numbers were a consensus of expert opinion, but in the latest edition, the WHO criteria changed substantially.

What the WHO is currently doing is to dispense with expert opinion, and just lay the numbers out for all to see.  Table II from the paper shows the numbers for men from couples who conceived within a year.  Take sperm concentration, for example.  For centile 5, the sperm concentration is 15 million per ml.  That means that only 5% of couples where the man had 15 million/ml sperm or less conceived within a year.  For centile 50, the concentration was 73 million/ml, meaning that 50% of couples conceived within a year when the sperm concentration was up to that number.  You get the idea.

The problem is that people like cutoffs, and in the latest edition, the WHO chose centile 5 as the line in the sand.  It’s a good number for thinking that below it, couple infertility likely involves the male.  But keep in mind that at centile 10, only 10% of couples conceived within a year.  In other words, having sperm numbers above the centile 5 cutoff doesn’t guarantee that the sperm are trouble free.

Frankly, I think the WHO numbers are most useful to get a ballpark idea of how fertility may be related to what’s inside the semen.  I prefer the approach David Guzick and colleagues took, where they applied a statistical method called Classification and Regression Tree (CART) analysis to sperm, which gives two cutoffs in a “green light, yellow light, red light” fashion.  For example, CART analysis came up with 13.5 million/ml and 48 million/ml for sperm concentration.  At 13.5 million/ml sperm or less, the “red light,” couple infertility likely involves the male.  At 48 million/ml or more, your sperm probably are “green light” good to go.  Between 13.5 million/ml and 48 million/ml, the “yellow light,” sperm may or may not be the problem.  You can find the Guzick CART cutoffs here.

A lot of people, including doctors and fertility specialists, are confused about the new WHO cutoffs.  Expect a little consternation about them for a bit.

WHO Table II Distribution of values, lower reference limits and their 95% CI for semen parameters from fertile men whose partners had a time-to-pregnancy of 12 months or less

N Centiles


2.5 (95% CI) 5 (95% CI) 10 25 50 75 90 95 97.5

Semen volume (ml) 1941 1.2 (1.0–1.3) 1.5 (1.4–1.7) 2 2.7 3.7 4.8 6 6.8 7.6
Sperm concentration (106/ml) 1859 9 (8–11) 15 (12–16) 22 41 73 116 169 213 259
Total number (106/Ejaculate) 1859 23 (18–29) 39 (33–46) 69 142 255 422 647 802 928
Total motility (PR + NP, %)* 1781 34 (33–37) 40 (38–42) 45 53 61 69 75 78 81
Progressive motility (PR, %)* 1780 28 (25–29) 32 (31–34) 39 47 55 62 69 72 75
Normal forms (%) 1851 3 (2.0–3.0) 4 (3.0–4.0) 5.5 9 15 24.5 36 44 48
Vitality (%) 428 53 (48–56) 58 (55–63) 64 72 79 84 88 91 92

*PR, progressive motility (WHO, 1999 grades a + b); NP, non-progressive motility (WHO, 1999 grade c).