Dr. Goldstein explains how Dopamine Fits in with all of the pharmacology strategies. Dr. Irwin Goldstein has authored more than 325 publications in the field of sexual dysfunction, with 20 consecutive years of funding by the National Institutes of Health in this area. He is Editor-in Chief of The Journal of Sexual Medicine, the official journal of the International Society for Sexual Medicine.
In the paradigm of diagnosis and treatment of a woman with a sexual health problem, we have a recognized strategy. It involves identification of the sexual health problem, and we would do a history, a physical, we get the psychologist involved to get a psycho-social history. We would do physical examination; that is an extensive one involving vulvoscopy with photography where we show women the image on the plasma TV so they can see what’s going on. We would do a speculum examination to assess the inside of the vagina. We would do a wet prep to see what bacteria that was there or not there. We would measure the pH of the vagina. We would, if we have access to sensation testing, we would do that. We would do perineometry so we can see the muscle strength around the vagina. We would measure bloods for hormones. We would, if needed, measure blood flow.
So there is a paradigm for evaluation. Having gone through the evaluation, whatever didn’t appear normal we would then have an educational interaction session with the patient and hopefully with partner: This is what we did in the evaluation, this is what we found wrong, what does all this mean, and then we’ll say okay, with this information we think these are your categories of diagnosis. We think there is a pain problem, we think there is an arousal problem, we think there is a desire problem, we think there is a lubrication-arousing problem. So now we need some strategies.
So the first treatment strategy is called modification of reversible causes. So we’ve gone from identification through education now to modification. So we could do physical therapy and modify the tone of the pelvic floor. We could do sex therapy and take the patient into strategies that avoid fear and anger and make the person more receptive to sexual strategies. We could take a medication like the birth control pill and find an alternative medication. We can take hypertensive, antihypertensive agent and try something different.
We can do diet, we can do exercise; all of these things have been shown to be beneficial. We can get involved in yoga, we can get involved in other strategies for relaxation; that’s modification of reversible causes.
Physical therapy. We need to talk about physical therapy. They have all kinds of strategies to either relax the high tone or strengthen the low tone kind of patient. Then we can get into outside of modification into what we call first-line therapies. There’s hormonal and non-hormonal, and based on the blood tests, we will identify if there are estrogen deficiencies, progesterone deficiencies, DHEA deficiencies, testosterone deficiencies, thyroid problems, and on and on.
So based on the hormonal issues we will either manage the hormonal problems. Then there is non-hormonal strategies, and that would be vasoactive agents that would increase blood flow if that was a problem or there would be dopamine agonist. So this is the lead end for the dopamine agonist question.
Dopamine agonists have been shown to facilitate the sexual reflex. In the brain there are a series of sexually inhibitory and sexually excitatory neurotransmitters. The sexual inhibitory neurotransmitters are serotonin and another one is prolactin. The ones that are sexual facilitators are dopamine, oxytocin and norepinephrine.
So strategies that raise the facilitators would allow somebody who had a low interest, low orgasm, low lubrication to improve that status. We have an interesting cohort of women where the sexual arousal is fully uninhibited; it happens all of the time, 50, 60, 70 orgasms a day, very distracting, very discomforting, unwanted, unremitting, near suicidal is the response of many of these patients.
But they lack inhibition. So there is missing relationship of facilitation and inhibition. So we have a bell-shaped curve; most people are in the middle, some people are hyposexual, and some people are firing that reflex all the time.
So for women who have low sexual desire and we recognize that one of the neurotransmitters which is dopamine can facilitate the reflex, pharmacologic strategies to raise dopamine called, so-called class of drugs dopamine agonists, would improve the sexual response.
So there are a series of dopamine agonists that we currently have, one of them being Bupropion, comes under the trade name Wellbutrin. It’s been long time recognized to reverse some of the bad effects of the SSRI antidepressant class. So we recognize dopamine agonists are very useful, but in women who are not even on SSRIs, Bupropion has been shown to improve libido and facilitate orgasm.
The new drug that we spoke of earlier that has an opportunity to be released, the Viagra for women, has as part of its profile, dopamine agonist activity. It also has norepinephrine agonist activity and it turns off the inhibitor serotonin. So it has three actions to facilitate the sex response.
So CNS drugs are drugs that work on changing the excitation/inhibition current sort of balance, and other dopamine agonists that are currently available would be any of the Parkinson’s drugs, the role of a Parkinson’s drug is to raise dopamine specifically in the substantia nigra of the patient who has Parkinson's, but in general it will raise dopamine.
Some Mirapex, Requip, drugs so we now also use for restless leg syndrome will improve sexual function. We have drugs that, one class is a class called Cabergoline, the trade name is Dostinex. It is used for men and women who have tumors in their brain that release prolactin. It turns out that if you raise dopamine you lower prolactin. Again, prolactin is inhibitory, dopamine is excitatory, so raising one lowers the other.
So you can actually stop the effects of prolactin by taking this drug Cabergoline, but in and of itself, Cabergoline and non-prolactin tumor patients will increase interest.
So we heard at our meeting in San Diego CNS physiology, CNS pathophysiology and CNS pharmacologic strategies, there is a room for multiple different drugs targeting all different kinds of locations of the brain, really cool, very exciting. We’re off a few years from that, but the lecture was just exhilarating with other new possibilities.
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