Posted by Jeff Berk, BOLT International;
So let’s get started… This is Opuntia bigelovii, better known as “Teddy Bear Cholla”. There is a legend, upon which I’m going to embellish, that suggests that during one of the Arizona prison breaks, the unfortunate inmate made it out of the safety of his confines and into a clumping of these cuddlies. The story goes that it was many hours before his rescuers could extract him, and many more hours after that before they could extract all the spines that he brought back as souvenirs of his time away.
Which brings me to unmet needs and endpoints in the treatment of Female Sexual Dysfunction. What does this have to do with Teddy Bear cholla, you ask. Not a heck of a lot. But A) I wanted to post that particular photo tonight, and B) I’m still on my “Everybody at FDA is a retard” soapbox. And FDA’s refusal to approve testosterone for FSD is just one more data point to prove that case (As if I need another data point on that point. BTW, there are a LOT of website hits coming in from Silver Springs, so if I stop blogging, I’m counting on you conspiracy theorists to chirp up.)
So, where was I … Oh yeah. Female sexual dysfunction…
- There is a tremendous disconnect between the demand for therapeutics for female sexual dysfunction and FDA’s interest in approving them. BOLT’s Female Sexual Dysfunction Panel wants to see two distinct clinical endpoints for FSD: libido (interest, desire) and responsiveness (time to orgasm, arousal).
“I am very interested in the large volume of women who feel that they have serious enough sexual dysfunction to be willing to be in clinical trials. We are doing a number of clinical trials of every kind of medication you can think of for women with sexual dysfunction. We advertise once in the newspaper and we get lots of calls. I keep thinking we are going to wear out this market but it isn’t true”.
“Because nobody (at the FDA) gives a #&@*”.
“Thinking in terms of the clinical trials we are part of, when we recruit for libido dysfunction we are getting younger women and when we recruit for orgasm dysfunction we are getting older women. I am trying to think whether they were all post-menopausal or not”.
- For premenopausal through early post-menopausal women (those in their 50’s) lack of interest is the most relevant complaint. Here, FDA’s endpoint of “increased number of satisfying sexual encounters” is relevant.
“When we recruit we don’t recruit by age and they are the ones who come in for (lack of libido). Some of them are as young as 25-30”.
“I do believe it is a huge problem that women are actually quite willing to talk about but probably most of their doctors are not. I am not impressed that all of these women are estrogen deficient. A lot of them are not. A lot of them just don’t have any interest in sex. So they are premenopausal women who just don’t have any libido”.
“I think it is just like men. Hardly ever are we “just like men” so I find myself surprised I just said that. Some women just aren’t interested in sex. They are not interested in sex. They are not interested in sex with their husband and they claim they are not interested in sex with anybody else and these are women who were not dysfunctional all of their life. That is a group that I don’t know what to do about. Those, I send them to somebody else”.
“Let’s talk about the post-menopausal women and divide them into the 50’s, 60’s and 70’s. Women in their 50’s the clear issue is interest. And that interest seems to fall off even before menopause, sometime in the late perimenopause but is persistent and continues throughout the 50’s”.
Time to Orgasm
- For older women, time to orgasm is a more relevant endpoint than “satisfying sexual encounters”. Older women who are sexually active tend to have had satisfying sex lives when they were younger. Natural aging processes, injury (damaging deliveries / peritoneal surgery), and the side effects of pharmacotherapy (SSRI use for depression) deteriorate both their function and that of their partners. For both their tissues are less responsive and there is less engorgement of genital tissue. It becomes harder for the men to stay erect and it takes longer for the women to climax.
“So the ones who had a reasonable interest in sex and flirting when they were single or more and had a good sex life those are the ones that I see a lot of. If the husband spends long enough at it they can have an orgasm or if they spend long enough at it they can have an orgasm, so they are low to orgasm. And that maybe one of the reasons they are not interested, they just don’t want to spend that much energy. And then there is another one of another group who claim that they are as interested as ever but it is very tiresome to get to orgasm and that may or may not be the same pathology”.
“Some of them have had probably very damaging deliveries or peritoneal surgery after delivery. I have seen two bike riders who that was the most plausible diagnosis. You can usually find another reason in about half of them and the other half may be having painful intercourse, maybe estrogen deficient but there are a lot of them out there. Some of them are on SSRIs which I guess are notorious for that”.
“From the female side, the problem even if there is interest that is the same as the male’s the tissues are less responsive, there is less engorgement of genital tissue and the clitoris so it takes them longer to get to orgasm and the orgasm is typically less intense. That is the same as a guy that gets increasingly less erectile function and increasingly longer to get that erectile function. And these are the natural processes of aging. The problem is that men can fix it very easily with the PDE5 drugs and women need to have adequate hormones, adequate initation and interest and the PDE5’s also have some effect also”.
“Men continue to have relatively normal erectile function in their 50’s with increasing amounts of mild erectile dysfunction in their late 50’s, very late 50’s, and that erectile dysfunction which is mild and very well described as a natural process of aging if you will. It is associated with an increase in premature ejaculation. Perhaps as much as 20% in the population around age 60. So if you have premature ejaculation obviously you are not going to have very much coital activity and a lot of women never had orgasm during coitus anyway”.
“Yeah, I agree. I don’t know any science about it but I agree (that SSRI use delays orgasm). I have heard a lot of patients tell me that but I am not the person who put them on the SSRI so I tell them they need to go back and talk to that doctor about it”.
- Pharma has not targeted time to orgasm as a clinical outcome (but we think that somebody should). One possible explanation is because this population is smaller than the younger population who lacks desire. Another is that the companies have not understood that this unmet need exists.
“I think if women thought that they could have a nice experience in a relatively short period of time that would be a winner. A lot of them also have by the time they get to be 60 and 70 when this becomes a really common complaint, they are slow to orgasm, a lot of them have husbands that can’t hang in there that long anyway. They are lucky to be able to get their own ejaculation. It is a tortuous problem. I think off the top of my head I would say that at least speaking for women over 65 that getting an orgasm faster would be attractive. But many of these women can produce their own orgasm because they know exactly what to do and they are much more efficient at it than their older husbands maybe ever were”.
“I would say that for women in their 60’s and 70’s it is a meaningful endpoint to them and their partners. But recognize no one wants to study those women because you have got way too many variables besides the normal sexual function variables, including vascular issues, hormonal issues, etc, plus the population that is having sex is shrinking. So if you are looking for a good turn on investment you don’t want to study those people either. I really mean that. If I have a married couple and they are in their 60’s and she is in her 60’s she comments exactly the way you do. And even if it is not a couple. The comments I get are things like I am going to buy stock in Eveready because I am burning through the batteries in my vibrator before I get to orgasm, that kind of thing. I think that is all real. I didn’t say it was pathological, I said it was real”.