Ovarian Function May Be Associated with Lifespan

Pharmacy Times welcomes back Daisy Robinton, PhD, co-founder and CEO of Oviva Therapeutics, to discuss female longevity and the impact of ovarian function on long term health outcomes. Robinton dives into the general mechanisms related to ovarian function, new innovations and areas of research to prolong ovarian function and push back menopause, the association between menopause and lifespan, and ways in which pharmacists can advocate for women’s health and recognize gender-associated adverse events. Robinton will be presenting about women’s health at the first Livelong Summit, happening on March 15 and 16 in West Palm Beach, Florida.

PT Staff: I would love if you could talk a little bit more about the research and the innovations your team is doing.

Daisy Robinton, PhD: The premise behind the work that we're doing as the kind of first pass approach to this is that the decline in ovarian function that women experience at midlife is driven, in part, by the fact that we run out of eggs. All women have what's called an ovarian reserve— that's the number of eggs that you have at any given point in time. Interestingly, the peak the highest number we ever have is in utero at 20 weeks’ gestation, when we're in our mother's womb, there's about 6 to 7 million eggs. At that point in time, that drops to about 1 million once we're born. And then by the time a female hits puberty, she has about 300 to 500,000 eggs remaining, and between puberty and menopause there's a steady loss of those eggs with each menstrual cycle.

Our hypothesis is that, if you can lower how many eggs we lose over time, it extends your runway to menopause. And there's a hormone that our bodies naturally produced called anti-mullerian hormone (or AMH), that is the master controller of how many eggs are leaving the ovarian reserve at any given point in time to enter that in a pathway to potential ovulation. And so that's the therapeutic strategy we're using— using AMH as a mechanism to preserve our ovarian reserve for a longer period of time and basically have more years where we're deploying eggs.

Each egg is housed in a follicle, and those follicles are what are producing the hormones. So as long as you have that kind of folliculogenesis, it's called— the follicles that are leaving the ovarian reserve to produce that one egg—[and] as long as you have that process moving regularly, you're having the hormonal milieu that's required for homeostasis. And so that's the work that we're currently developing to hopefully provide at least at least one but I'm hoping a suite of therapeutics that offer women, different intervention options for preserving their ovarian function.

PT Staff: From what I'm understanding, and please correct me if I'm wrong, this would be something you would start doing fairly earlier on in perimenopause. Would [this] even be something that someone in their 20s or 30s would start taking in order to prolong [ovarian function? What does the timeline looked like?

Daisy Robinton, PhD: The intervention time is something that it depends a little bit on… the outcomes you really want. So certainly the earlier that you intervene I think the better in terms of the longer-term benefit and how much you can influence the ovarian reserve when you're, let's say, in your 20s, versus when you're approaching menopause, when you're sort of having an accelerated rate of decline in your ovaries.

Anyways, that being said, we have a really beautiful dataset that my co-founder David Pépin published last summer in Nature Communications, where they used a recombinant form of AMH, much like the one we're developing for clinic, in cats as a means to provide durable contraceptive.

I can very much see this as something in the future as we get further along in the development that could be offered as a contraceptive at a younger age. I think I started taking birth control pills at age 17 or 18 and was on them for probably 15 years. That would be a lot of eggs to save, if that whole time I'd been preserving ovarian reserve instead of losing 1000 eggs every month, but not ovulating. So certainly, there's a use case for a younger woman taking it if she wants to use it as a contraceptive or if she wants to preserve ovarian reserve. But I think obviously the longer that you're intervening and taking any sort of therapeutic, you have to appreciate what are the risks of doing something chronically like that? And we just we don't we don't know right now.

PT Staff: In your opinion, does this impact like the ability to develop certain cancers or does it slow down like different frailty may be like different things that contribute to poor aging?

Daisy Robinton, PhD: So what I can say about the longevity piece here is what we already know is that women who enter menopause later tend to live longer, and those who entered menopause earlier tend to have shorter lifespans. There's also some really cool data showing that if you take an ovary out of a young mouse and transplant that into an older mouse, you can see lifespan extension, so longevity extension by 6 to 11% in the transplant recipient, and the effect size (so how long that lifespan is extended) is directly proportionate to the relative youth of the ovary transplanted. So there's certainly a linkage that's causal between the sort of youth and function of an ovary and the host of that ovary.

The downstream effects of losing one's ovarian function directly impacts health in a number of ways that I detailed earlier in terms of the cognitive function, heart health, and a lot of other aspects. So, I'm sure many of those things we'd see improvements on if we can extend the number of years that a woman is pre-menopausal.

PT Staff: How could pharmacists, other providers, and even researchers and people in politics advocate more for women's health research and support, not only for the research being done but accessibility to it and accessibility for participants in this research?

Daisy Robinton, PhD: For those in the United States today, it feels like the most powerful thing we can do is vote. I think this actually on the ballot in many ways, our ability to make choices for ourselves and our health is at risk right now in this country.

I think a big way to advocate for women's health is to support policies and politicians that recognize that many of these choices around abortion and access to fertility care is really something that a patient should decide with their doctor. Aside from that, I think that as a pharmacist, you're interfacing with patients and providers for that matter and I think that really doing some legwork to the degree that you can understand whether there's nuance in some of the drugs that you might be handling or offering out between the sexes (sometimes they have data, sometimes they don't).

Understand that so when you do have that touch point with the patient, you can say, “Hey, this has been shown in women to etc..” which is most likely something the doctor hasn't shared— in terms of if there's differing effects between men and women, or if there might be some evidence to support that.

I think that's a huge piece that could be meaningful and really powerful. Even to just acknowledge the possibility of that to either the patient or the provider, "Does this work differently in men and women?” If asking that question, they certainly stand in a position to be able to promote awareness of that fact and ask for that information and want to know it and I think a big piece of the solution is this sort of hunger and awareness that we're seeing. An increase in better understand[ing] how we care for males and females, I should say, and the different physiology we present.