Dr. Sarrel explains what a woman should consider before she sees her physician for hormone replacement therapy.
Well, what you are bringing up is a very important piece of information to know about testosterone. You noticed that a moment ago when I said what tests should be done, I mentioned the test called a bioavailable testosterone, and that’s an important concept.
When we started this discussion, I talked about the hormone being made in the gland, released into the bloodstream, and carried to cells throughout the body.
Well, the way in which the hormone is carried to cells is attached to a protein. So we actually have a phenomenon which is the binding of the hormone to a protein called a globulin. Most people have heard of globulins. They are made in the liver and they are proteins, and the globulins that transport testosterone are called sex hormone-binding globulin, or for short SHBG, and this is a concept that a woman should know before she goes for help.
And the reason is this: Most of the testosterone in the body is bound to SHBG and is not available to act in the cells of her body. Only two percent is actually available to do all these things that testosterone does; 98 percent is tightly bound to these circulating globulins, these transport proteins, and can’t do anything.
The reason I mention it is, there are situations in which a woman could be making normal amounts of testosterone but have too much SHBG, and as a result she has no free testosterone. The most common is low-dose birth control pills.
So we have the interesting phenomenon in our country, quite widespread, of young women in their teens and in their 20s who have an active sex life, have started on oral contraceptive and are taking one that stimulates the binding globulin, and they may be able to respond sexually, but they have no desire.
I have been working with Yale students, undergraduate and graduate students, since 1969. In the 60s and 70s and early 80s, we never saw this problem. It’s only with the development of the newer, lower dose birth control pills that stimulate high levels of SHBG that you can have a 24-year-old coming in and saying, “Gee, I have no problem with my boyfriend or my fiancé. I have always been enjoying my sex life, and now I have no sexual desire,” and invariably her problem is a high SHBG, and a very low free testosterone.
And there’s another situation; it happens in women who have either lost their ovaries with surgical menopause or have had a natural menopause, and the hormone that’s most commonly prescribed for their symptoms like hot flushes or vaginal dryness or sleep disturbance or palpitations.
Most commonly the women are given an oral estrogen, and typically those women when they first come in complaining of hot flushes are not complaining of a loss of sexual desire, as a matter of fact. And this is an important part of the story; estrogens stimulate the liver to make SHBG, and when estrogens are very low, the woman can have an elevated free testosterone.
Sometimes their complaint will be of being hyper-sexed, and that doesn’t feel comfortable either. Sometimes the complaint is of having angry outbursts or being irritable all the time, and that’s from too low an estrogen and too high a free testosterone.
Well, when a woman starts on an oral estrogen, it will stimulate the liver. And by three months we know from many studies, including two of my own, but many others have shown the same thing: the oral estrogens stimulate the liver to make twice as much SHBG. It doubles in three months.
So in fact a woman could come in at the beginning and say, for let’s say sex is the issue, and she says, “I have a problem of vaginal dryness and pain with intercourse,” and the doctor gives her the estrogen. She now has normal blood flow; the atrophy disappears. She can have intercourse without any pain, but she lost desire. Why?
Because in those three months, the oral estrogen stimulated the liver, made too much binding globulin, and now she has got too little free testosterone. Isn’t that an interesting story? And it’s something the woman should know before she starts.
Other approaches to hormone therapy, obviously there are other kinds of birth control pills that don’t give as high an SHBG and so can bring it back down to a normal level. So it’s a matter of substituting one birth control pill for another, and similarly, for the woman whose liver makes too much SHBG from the oral estrogen, she can be switched to one of the non-orals like a gel of estradiol or a patch of estradiol or even a vaginal estradiol for her menopause symptoms, and the SHBGs will come right back down.
It’s also interesting that when you give estrogen plus testosterone that lowers the binding globulin itself. So the combination of giving it, giving testosterone, and now we can go on to this issue of well, what’s available, but giving it will also get at the issue of two lower level in two ways.
One, it gives the extra, but two, it lowers the SHBG, and we have actually done that with young women, women like Yale graduates or undergraduates on birth control pills, who don’t want to stop their birth control pills, so we have supplemented them with a low dose of an estrogen-androgen combination, and then they are fine.
About Dr. Sarrel, M.D.:
Philip M. Sarrel, M.D., completed his medical education at New York University School of Medicine, his internship at the Mount Sinai Hospital, and his residency at Yale New Haven Hospital. In addition to his many years on the faculty of the Departments of Obstetrics and Gynecology and Psychiatry at Yale University School of Medicine, Dr. Sarrel has also been a Faculty Scholar in the department of psychiatry at Oxford University, Visiting Senior Lecturer at King’s College Hospital Medical School at the University of London, Visiting Professor in Cardiac Medicine at the National Heart and Lung Institute in London, and Visiting Professor in the Department of Medicine at Columbia University College of Physicians and Surgeons in New York. He is currently Emeritus Professor of obstetrics, gynecology, and psychiatry at Yale University.