A model predicts up to 47 years of delayed menopause after ovarian tissue transplantation; Maria Marinova asks whether the organ could function in an aging body
A model predicts up to 47 years of delayed menopause after ovarian tissue transplantation; Maria Marinova asks whether the organ could function in an aging body
On October 15, aging biologist Maria Marinova published an essay examining which functions medicine would need to restore for menopause to count as solved. She compares transplantation of frozen ovarian tissue, hormone therapy, drugs, and lab-grown tissue. The 47-year figure comes from a model with specified assumptions about age, follicle reserve, and transplantation strategy.
The ovary holds a finite reserve of follicles, the structures in which eggs develop. As this reserve runs out, menstrual cycles and hormone production change. One woman may prioritize bone protection and symptom relief; another may want to maintain her own hormone production or the ability to have children. Different interventions therefore need to be assessed against different outcomes.
One strategy is to preserve some ovarian tissue in advance and transplant it back later. In the model by Johnson and colleagues, a woman with an average follicle reserve at age 25 preserves a quarter of her ovarian cortex. If 40% of the follicles survive transplantation, the predicted delay in menopause is 11,8 years; with 80% survival, it is 15,5 years. The model predicts a delay of up to 47 years with 80% follicle survival when the tissue is returned in three or six separate transplants. Some follicles die while blood vessels grow into the transplanted tissue, and these losses affect how long it can function.
Transplanting a woman's own tissue replenishes her follicle reserve, while hormone therapy relieves symptoms and protects bones. Rapamycin has been studied as a way to slow depletion of this reserve: in a Columbia University trial, 50 women aged 35–45 received low doses of the drug or a placebo for 12 weeks. The primary outcome was anti-Müllerian hormone, a marker of ovarian reserve. These interventions act on different parts of the same system.
A functional ovarian substitute has already been tested in mice. In a 2017 experiment, researchers seeded a porous gelatin scaffold with mouse follicles and transplanted it into animals whose ovaries had been removed. The scaffold retained the follicles, blood vessels grew into it, and hormonal function was restored; the mice produced offspring and nursed them. The experiment shows that an implant must maintain the tissue, establish a blood supply, and integrate into the body's hormonal system.
The hypothalamus in the brain and the pituitary gland at its base control the signals the ovary receives. Ovarian transplantation experiments in mice showed that a young organ sometimes restored cycles in old animals, although the aged hypothalamus and pituitary often limited the effect. Ovarian hormones act on bones, blood vessels, the brain, and other tissues. Marinova closes her essay by framing the task in terms of how an entire system of organs functions:
“We may find that replacing an aging ovary is the easy part.”