I don’t know when my love for science started. It was probably inevitable, living in a medical family and raised by two determined, compassionate and visionary women; my mother and grandmother. Their stories and those of powerful women bravely balancing their professional and private life inspired me to understand the secrets behind fertility and menopause.
For the most part of human history people had no word for menopause, and it was merely recognised as a transition to the status of elder, grandmother. During the 19th and 20th centuries the male dominant medical community made menopause a taboo. Sigmund Freud wrote that “It is a well-known fact … that after women have lost their genital function their character often undergoes a peculiar alteration” and they become “quarrelsome, vexatious and overbearing”. Psychiatrist David Rueben weighed in…”Once the ovaries stop, the very essence of being a woman stops…she is no longer a functional woman.”
Despite the advancement of our medical understanding of menopause, it is not nearly enough. It is still a taboo topic, as if stamping women with an expiration date.
The clock on your ovaries
Menopause usually occurs naturally in women during their late 40s or early 50s, and signals cessation of a woman’s reproductive ability. It also exposes them to risks of later life diseases such as cancer, heart disease, and osteoporosis.
The story starts when a woman is a foetus. This is when she possesses the highest number of ovarian follicles. However, at about 16 to 20 weeks old this number starts declining via an irreversible process. The speed of the decline and the size of the initial follicle pool we were born with ultimately determines when menopause occurs. This makes a woman’s reproductive window, or fertile period, individual and largely dependent on genetic and environmental factors. The decline in the number of oocytes, the seeds of human life, is accelerated in the 10 years preceding menopause. It affects the quality of the ovarian reserve resulting in clinical subfertility and increased miscarriage rates in women of advanced maternal age. However, menopause does not occur the moment of the onset of irregular or absent menstrual cycles. This process is initiated much earlier, for some ladies even 10 year before. In specific cases of women with primary ovarian insufficiency, this can happen before the age of 40!
The most challenging aspect is that the current markers used in clinical practice can only determine the timing of menopause just before its onset and do not reflect the quality of the oocyte. This makes early prediction, treatment, and family planning impossible.
Two fertility trends of the 21st century are evident in the Western world; women are having fewer children and at a later age than in previous centuries. This in part has led to increased demand for reproductive assistance. The average age of women seeking assisted reproductive technologies in 2017 was about 36 years.
Assisted reproduction treatment cannot compensate for the natural decline of fertility with age. What we need is comprehensive understanding of the mechanisms behind female reproductive aging to uncover the genetic and environmental factors that define the onset of menopause. This is precisely what I do.
The genetic barcode and its secrets
All the instructions that guide our body are encoded in 4 letters, called nucleotides, which come in unique combinations making us who we are. Think about it as an individual barcode – your genome. These differences guide one’s fertility journey and reproductive aging, bringing menopause to some in their 40s and others at their 50s. By combining disruptive, state-of-the-art genomic technologies with genetic epidemiology (study of the role of genetic factors in public health concerns in a given population), I analyse the genomes of almost half a million women to identify mechanisms and genetic markers that drive them into earlier menopause and guide their fertility.
This might help us develop effective interventions in the treatment and prevention of early ovarian failure, and predict individual reproductive window. This gives women the opportunity to plan their reproductive journey and family in advance.
The age at menopause relates to many aspects of human health. Thus, the discovery of genetic markers may also yield needed breakthroughs in understanding the genetic variation conferring risk of diseases at later adulthood.
Studying this subject, I realised how deeply menopause is implicated in the human condition and how questions about menopause involve even more serious discussions about the nature of humanity, the structure of our society, and the relationship between men and women.
Illustration is by Cambridge-based artist Naomi Davies. Here’s what Naomi says about it:
“When I heard about Stasa’s work, it got me thinking how much our uteruses affect us. They cause us pain, joy, discomfort, annoyance. They are part of our birth and can be part of our death. Fertility, or lack of it, can affect our lives. For trans people, the existence or non existence of a uterus can be crucial to how others define them. So I decided to draw Stasa’s lab with a difference. The lab workers have their uteruses visible, if they have one. There’s a uterus with a foetus, a uterus in a trans person, a uterus after surgery, etc. Even Stasa’s uterus (or at least, my artistic impression of it!) is there for us all to see. The uterus is usually hidden, but hugely important.”
Una, writer and educator
Radu Toma, Romania
Financier and CEO, USA
Letizia, Saudi Arabia
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