The Story of Testosterone

April 28th, 2010 § 18 comments

When you think of what makes up the inside of the testes, think spaghetti. Imagine a bunch of spaghetti noodles squished together. Inside of the noodles are the developing sperm cells. Between the noodles are cells called “Leydig cells” whose job it is to make the male hormone testosterone. They start with cholesterol, and churn out testosterone.


Not only is testosterone critical to the factory inside the spaghetti that makes sperm, it is important for many parts of the male body to work well. Adequate testosterone is needed for bone and muscle strength, and men with low testosterone may experience low sex drive, problems with mental focus and depression.

The relationship between testosterone and how the penis works is less clear. Men with low testosterone can get erections, but of course sex drive can be a problem. And if a man’s testosterone is low, correcting it may improve the performance of drugs like Viagra, Levitra and Cialis.

Total testosterone doesn’t tell you the whole story. Testosterone circulates in the blood in two forms. Testosterone that is either free or loosely bound to blood protein is called “bioavailable”, and as the name implies, is available for the cells to work. Testosterone that is bound to sex hormone binding globulin (“SHBG”, but also called androgen binding protein,) is blocked from acting in cells. Although many labs offer to measure free testosterone, often the most reliable way to measure bioavailable testosterone is to have the blood tested for albumin, sex hormone binding globulin and testosterone, and then to use a calculator for bioavailable testosterone. One is available on the International Society for the Study of the Aging Male’s web site, and another for iPhones and iPod touches can be found in the iTunes store. A man may have adequate total testosterone, but still suffer from the ravages of low testosterone levels if his bioavailable testosterone is low.

Testosterone levels rise and fall during the day, with a peak in the early morning, and the lowest point in the late afternoon. That’s why many a man’s sex drive is highest in the morning, and it’s time for a nap in the afternoon.

Testosterone is converted to dihydrotestosterone, which makes the hair fall out of your hair follicles if your family tree has male pattern baldness. Dihydrotestosterone also enlarges the prostate. Drugs like finasteride (Propecia and Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone.

All men have a little estrogen, the female hormone. An enzyme called “aromatase” converts testosterone to estrogen. If the estrogen level is too high, it may interfere with the working of testosterone.

One last important point about the making of testosterone: levels in the testis are twenty times greater than in the blood. So if a man is given testosterone, his blood levels may increase, but the pituitary tells the testis, “hey, there’s enough testosterone around, so stop making it.” As a result, testosterone levels in the testis fall, sperm stop being made, and the testes shrink. That’s why many body builders who take testosterone and other similar chemicals experience shrinking testes. Testosterone can be great for men with low levels later in life, but for men who want to have children, it can really work against sperm production.

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§ 18 Responses to The Story of Testosterone"

  • DR. M K BEHJATI D, MD says:

    Hi DR niederberger
    you were one of my teacher.
    you explain one of my need easily.

  • Wes says:

    Hello Dr Niederberger, what do you think about natural HGH supplements to help with low testosterone? What could such a combination of clomid and HGH be like to the male body? Harmful, or could such work together to raise the levels of testosterone faster and naturally? Why don’t doctors combine natural and meds more? Thanks.

  • Wes says:

    I’m speaking about natural supplements that help your body’s own human growth hormone production to increase its production naturally with a blend of herbs and such. A list of one natural product’s ingredients are: ‘a proprietary blend of amino acids such as chromium amino acid chelate, Colostrum, L0tyrosine, L-Ornithine HCl, L-Lysine HSL, L-Glutamine, L-Arginine HCl, Anterior Pituitary and Phosphatidyl Choline’.

    Basically, do you think well of these methods as a way to naturally increase testosterone levels by increasing one’s hgh production and release?

    If so, what about taking such things in conjunction with clomiphene? I take neither, but was wondering if such a combination would stem off dependency of the body upon clomiphene, or any other medication, if at the same time one was taking natural things to naturally increase the body’s own production of hgh/testosterone. I suppose that this would be for a person that was very low to start with, and needed medication to help regain much higher levels.

    This is in response to the comment in the FAQ, ‘Logically, you’d think that when someone stops taking a drug, like a medication to increase the production of testosterone by the testis, everything would return to the way that it was before the medication began. But what happens after a drug is stopped can be different than before it began, for better or for worse, and is different for each man.’. I just thought that to do both (natural and clomiphene) might stem off any dependency of the meds or a return to bad levels when meds are stopped…but didn’t know if such would be dangerous? Thanks.

    • maledoc says:

      Without controlled studies, it’s difficult to predict outcomes. But I can’t think of a biological basis why those particular chemicals would interact with clomiphene to increase testosterone in a male on a typical well balanced diet.

  • neicholai says:

    Thanks yall is there any better fertility drug than clomid??

  • Wes says:

    What is your thoughts on the long term negative effects of Avodart? Many user are now reporting some terrible side effects to libido and wild changes in their hormonal system. I’ve read about doctors trying all kids of methods to block the negative feedback loop and/or trying to restart the natural production.

    • maledoc says:

      Hi Wes, side effects of medications are typically idiosyncratic, meaning that you can’t predict exactly what side effect could happen for a particular man or necessarily understand why it happened. Sometimes what seems like a side effect is something unrelated to the medication that happens to be happening at the same time. That’s why when a commenter on this blog asks or tells about side effects, I write that men experiencing them really need to talk to their doctors about them, because they’re different and have different reasons for happening for each man.

      • Wes says:

        A class action law suit has taken place against Avodart, due to the real and numerous harsh side effects. This is much more than a few people with idiosyncratic symptoms.

  • Wade says:

    If testosterone is required throughout the body, what controls its distribution and can that distribution be controlled or focused on a particular area?

    • maledoc says:

      Testosterone is distributed throughout the body via the blood system. But locally it can work differently as cells it encounters may have more or less of its receptor (the androgen receptor) and whether it is converted to dihydrotestosterone. (Put “dihydrotestosterone” in the search box and you’ll get a couple of places where I mention it. I should probably write a post on it at some point.)

  • Wade says:

    Thanks for your response doc. I may be over simplifying it but does that imply increasing the androgen receptors in the Leydig cells would yield a higher sperm count? Or at least help facilitate production?

    I also read your entry from 2003 in The JoU regarding alternative medicines and was curious if the last 10 years provided any useful data?

  • Wade says:

    Correction – Sertoli cells

  • Mike B says:

    Regarding the possible side effects of Clomid, like Gynecomastia, or enlarged Pituitary or other visual issues reported like ‘floaters’, how soon can these effects occur? Are any of them irreversible?

    • maledoc says:

      Hi Mike, side effects are fairly infrequent and sporadic, so the answer to the question is at any time, and sometimes. That’s why it is so important for a man to work with his doctor in treatment. I also encourage you to read the other posts on this blog and especially the comments, as many questions are answered and there’s great information there.

  • maledoc says:

    It’s been many years, and I’ve finally turned off comments for this WordPress blog. Why? Although it’s the first question in the FAQ, I still get comments (a bunch a day!) asking personal medical questions that I can’t answer. That’s sad and frustrating for me, because as a doctor, I really like to help patients. But this WordPress site was never meant to deliver personal medical care, and the University lawyers tell me that doing so would run afoul of State and Federal laws.

    If you have specific questions about your own personal care, I urge you as outlined in the FAQ to use the American Urological Association’s Society for the Study of Male Reproduction’s search engine

    I also urge you to read through all of and especially the comments. For the five or so years that it was active, A lot of excellent questions were asked, including by other healthcare providers. Chances are, if you have a general question, it’s been answered here and more than once.