When it comes to the use of testosterone for women’s health, Australia is among the world leaders. For this interview, Rachel Rubin, MD, spoke with Susan Davis, MBBS, PhD, an endocrinologist in Melbourne and a pioneer in the field of testosterone, about what her research has found and the evolving role of the hormone in clinical practice — and why current guidelines on its use are too rigid.
Rachel Rubin, MD: You published a large piece in The New England Journal of Medicine last year about female sexual function. What were the main takeaways of your article, which I and our colleagues in the field consider an historic achievement?
Susan Davis, MBBS, PhD: The journal wanted me to write about sexual function in women. That was a huge challenge — to try to cover the whole of female sexuality, from young adulthood through to older women, in a single piece with a word limit. It really made me think and focus.
One of the key messages was that the anatomy of the female sexual responsive organs and female genitalia was poorly defined until recently. So little attention has been paid to female sexual function and female sexual responsiveness. In fact, the anatomy of the clitoris, as you know, was only clearly identified in recent years. We still don't understand the pathways of female sexual responsiveness well.
Rubin: You’ve done a lot of work in testosterone, including helping to create global consensus and guidelines on the use of testosterone for women. How has your understanding of the hormone evolved?
Davis: One of the big problems with testosterone is measuring it. Traditionally, most of the studies in women have used immunoassays, which are what are used commercially in clinical practice to measure testosterone in the community. The same assay being used to measure testosterone in men is being used to measure testosterone in women.
The problem is, these measurements are too blunt, too imprecise. The work we have done, particularly over the past 10 years, has been to measure testosterone in large numbers of well-characterized women using liquid chromatography and mass spectrometry — high-precision measurements with which we can discriminate between different amounts in the blood with complete accuracy and repeatability. That's been in order to understand reference ranges in women by age and by circumstances — like if they've had their ovaries removed, the effect of menopause — and also to look at the relationships between blood levels of sex steroids, testosterone, DHEA, estradiol, and other outcomes, like desire, arousal, orgasm, and sexual self-image, as well as things like depressed mood and a sense of well-being.
Rubin: There is some indication that testosterone in women is helpful for hypoactive sexual desire disorder. Do you see the research on that expanding in the future? And where would you like to see the research on testosterone more broadly go?
Davis: There is irrefutable evidence from randomized controlled trials and placebo-controlled trials that testosterone will improve low desire in the majority of women, if that's a bother to them. Most studies of this effect are limited to postmenopausal women. But we've done two studies in premenopausal women between the ages of 35 and 45 who are bothered by low desire. The largest of them enrolled just under 300 women and found improvement in low desire in the latter reproductive years.
I would like to see more research in that space. I think that's critically important. But we're also looking at the effects of testosterone on bone in women under the age of 55, and on cardiac function and heart failure outcomes in postmenopausal women. And we're also doing a big study of testosterone and muscle function, power, performance, and mass in postmenopausal women. We're trying to better understand what role testosterone has in women beyond sexual function.
Rubin: How long has testosterone been approved in Australia for commercial use?
Davis: We have a lot of experience in using it in postmenopausal women. It was grandfathered in to one particular state, Western Australia, well over two decades ago. And because we have a national prescribing system, I'm licensed to prescribe anywhere in Australia. It's been available for 20 years, but it was officially approved by the regulators just on 2 years ago.
Rubin: Why do you think there is such a slow approval for this type of thing in the United States when we could use the data that have come out of Australia and this global consensus that exists? Why do you think there's such a difficulty with the regulatory system here?
Davis: Procter & Gamble went to the Food and Drug Administration in 2004 and were knocked back. Regulators agreed that the efficacy data were good, but the big concern was safety in terms of cardiometabolic health and the potential for breast cancer. Many companies subsequently have approached the FDA to have testosterone products approved, but there was always quite a lot of pushback and difficulty with the agency agreeing to what studies would be acceptable. And it just became a bigger and bigger barrier, the bar kept getting higher; and the cost of going through this process is massive, to the point of being a deterrent.
So rather than the FDA saying we have a problem here, we have all these people prescribing male formulations to women, no standard dosing. Women are potentially at risk; people are using implants with no good evidence of their efficacy and safety — all this compounded stuff. We feel there's a need for a licensed product to protect women.
Rubin: You've been very involved with writing guidelines. Where would you like to see the guidelines and the dogma change going forward?
Davis: I'd like to see the dogma about restricting age and years since menopause go away, because it's like somebody has drawn a line down the blackboard just where it seems to fit best, not for any particular reason. I think the guidelines need to be much more in line with clinical care and perhaps less dogmatic.
I also think we need more research on transdermal estrogen, and we need far more research on progesterone. A lot of claims are being made about progesterone being unhealthy, but we don't have enough data one way or the other. It appears to be incredibly safe, but I would like to see a lot more research.
Susan Davis, MBBS, PhD, is director of the Women’s Health Research Program in the School of Public Health and Preventive Medicine at Monash University, consultant endocrinologist at Cabrini Medical Centre, and head of the Women’s Specialist Clinic at the Alfred Hospital, in Melbourne.