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One hundred years ago, life expectancy hovered at about 56 years of age, roughly the same age as the onset of menopause, 51. And now, while the age of menopause has remained unchanged, our life expectancy has stretched into the eighth decade of life. For women, or individuals with ovaries, menopause is now the midpoint in our lives: 40 percent of our lifespan is lived in a post-menopausal body.
Though many herald the ending of periods and an end to worries around unwanted pregnancy, there remains the stark truth that our declining ovaries have a significant impact on our overall health and well-being. And worse still, there aren’t enough options to prevent or address the ailments that accompany menopause beyond hormone-replacement therapy (HRT) — an effective strategy that unfortunately is not appropriate for all women, and still bears a stigma from the early reporting of the WHI study — as well as some supplements and lifestyle choices shown to improve symptoms.
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Our ovaries age at roughly 2.5 times as fast as the rest of our bodies, and once we go through menopause the physiologic changes that occur result in significantly increased risks of cardiovascular disease, declines in neurocognitive health, mood and anxiety disorders, sleep dysfunction, immune dysfunction, sexual dysfunction, dysregulated glucose metabolism (including weight gain), and increased incidence of osteoporosis. During this time in life, droves of women leave the workforce or suffer silently through as many as eight hot flashes a day. It is estimated that in the U.S., women lose $1.8Bn of working time per year. This is not to mention the strain on relationships and family, and more generally the lower quality of life many women experience.
It’s time we do more to change this. It’s time for innovative solutions to offer women agency over when, or if, they go through menopause at all.
My foray into research was driven by my family history, including a number of family members who suffered with chronic diseases including Type 1 Diabetes, Alzheimer’s and dementia. I wanted to better understand the underlying physiology of how and why these things happen, and more importantly, how to stop them. After completing a PhD at Harvard University in human biology and translational medicine, I pursued a post-doc, and shortly thereafter — newly single — had my own run-in with doctors that changed my life.
Knowing that I deeply desired building a family, and considering the fact that I was single and in my early 30s, I decided to visit a reproductive endocrinologist with the aim to better understand my fertility, my own physiology, to inform my decision around whether or not to freeze my eggs. The visit with this doctor forced me to recognize an embarrassing truth: I knew very little about female physiology, about my own body, despite being (what I thought was) an informed, educated, empowered woman. And if I had so much to learn about this space — coming from a background in human biology — what did this mean for women across the country, for women all over the world?
In pursuit of more information, and to battle my own ignorance, I aggressively researched the scientific and clinical literature to better understand the women’s health landscape. I was shocked to discover the gaps of information, data, and readily-available resources across women’s health. I stumbled across disturbing truths, including the fact that until 2016 the vast majority of biomedical research has been done in male animals, or, how women often have much longer times to diagnosis, or are more often diagnosed for psychiatric conditions for physical symptoms. I was angered, and impassioned, by the lack of research and innovation around what is an inevitability for all women — menopause — especially given the negative impact on quality of life and health that most women experience. My journey to founding Oviva Therapeutics began.
The premise behind our work is that the ovaries are the fastest aging organ, and with their decline women experience significant declines in health and quality of life. A key driver of ovarian decline and menopause is the depletion of our ovarian reserve, or the number of eggs a woman has at any given point in time. At birth we are born with all the eggs we will ever have (roughly 1 million), and during a woman’s reproductive years she is losing approximately 1,000 eggs per menstrual cycle; this is regardless of whether or not she is on birth control. As a woman approaches menopause, the number of eggs in her ovarian reserve gets smaller and smaller until it hits a low threshold (thought to be 1,000), after which menopause is triggered.
To circumvent this decline, we are developing a therapeutic based on the naturally-occurring Anti-Müllerian Hormone (AMH). AMH is generally used by clinicians in fertility clinics as a proxy of ovarian reserve, and in our bodies it acts as a sort of ‘brake’ on our ovarian reserve — regulating how many of the eggs will leave the ovarian reserve at any given point in time and begin to mature for potential ovulation and fertilization. Higher AMH levels translates to fewer eggs departing the ovarian reserve, whereas a reduced AMH can lead to accelerated depletion of the ovarian reserve and shorter time to menopause. In fact, AMH levels are predictive of onset of menopause, and associated with an increased risk of early-onset vasomotor symptoms (like hot flashes). Increasing AMH levels therapeutically, which we are pursuing at Oviva, may delay or abolish these symptoms — as well as prevent menopause altogether. We aim to make menopause optional. We aim to give women choice over when, or even if, they will experience menopause.
While our programs are still in pre-clinical phase, we are encouraged by the early animal data showing efficacy in a number of settings, including improvements to ovarian stimulation for IVF and durable contraception. As we approach the challenge of performing clinical trials in humans, we are both optimistic and deeply motivated by our vision of a healthier future for women. Much like contraceptives in the ’70s, bringing this therapy to women offers the potential for greater choice in how we can manage our health and bodies, and importantly will give us agency over our lives throughout our lifespan.
We do not need to settle for today’s standard of care — we have the potential for innovative solutions that are better than what’s out there today. Ultimately, a successful AMH-based therapeutic that prevents ovarian decline could not only significantly improve women’s experience of aging, but have powerful impacts to her career, her family, her relationship with her body and her overall quality of life. And I think it’s well past time we bring that to bear.
*As a note, I use the term ‘women’ throughout this piece to describe women born with functioning ovaries, though I recognize that not all people with ovaries identify as women and that not all women have functioning ovaries. This wording is in no way seeking to minimize or dismiss people across the gender spectrum or women whose ovaries are absent or nonfunctional.
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