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By science journalist Antje Gerd Poulsen

The face flushes, sweat breaks out, and a window is hastily opened. Nighttime sleep becomes a rare visitor, energy is in short supply, and moods swing. This is how some women experience symptoms during menopause. Additionally, the decline in sex hormones can, over time, also impact health and lead to osteoporosis and obesity, with more body fat and less muscle mass, thereby increasing the risk of diabetes and cardiovascular diseases.

Postdoc researcher at Herlev and Gentofte Hospital, Ida Marie Boi Jacobsen, aims to prevent both symptoms and diseases by developing a safe alternative to oestrogen treatment. To support this work, she has received DKK 5 million through a “Frontier Grant” from the Lundbeck Foundation.

Many seek to avoid hormones

Menopause is not a disease, but the abrupt drop in sex hormones can, as mentioned, bring about illnesses. Today, treatment is primarily based on oestrogen, but many choose to opt out of hormone treatment.

“Oestrogen is a really good treatment, but there is a cancer risk if there’s a family history of breast cancer, so other options are needed as well,” says Ida Marie Boi Jacobsen.

The drug that she and her team want to develop targets the hormone LH (luteinizing hormone), which stimulates ovulation in women and testosterone production in men. The medication will work by blocking this hormone.

LH levels in women are normally low. They only increase around ovulation, but during menopause, the production of this hormone skyrockets. And there are indications that this might have serious consequences.

This was discovered by chance in connection with studies of another hormone with the same mechanism of action, explains Ida Marie Boi Jacobsen, who researched male fertility during her PhD.

“When healthy, normal men received this hormone, they excreted more calcium in their urine, and they produced more of a hormone that promotes the erosion of bones.”

The discovery sparked interest in investigating LH more closely. And that is exactly what Ida Marie Boi Jacobsen and her team have done in mouse experiments.

“Our preliminary data indicate a correlation between high levels of LH and osteoporosis and cardiovascular disease. But we have only shown this in mouse experiments and over a very short period.”

A special type of antibody

The grant gives her the opportunity, over the course of 18 months, to develop the idea and prepare a presentation for potential investors, in collaboration with a group of researchers from the Research Unit for Hormonal and Metabolic Diseases at Herlev and Gentofte Hospital.

Ida Marie Boi Jacobsen is especially pleased that the grant also includes professional mentoring.
“It gives me an entirely new understanding of what it takes to develop a treatment and to make investors see the potential. As a basic science researcher, this is a whole new world for me,” she says.

If it proves true that LH levels are a critical factor for symptoms and diseases in menopausal women, the hypothesis is that an antibody can block the hormone.

The researchers have spent nearly two years finding such an antibody, and it now needs to be fully developed and engineered with a specific function, in collaboration with experts from the Technical University of Denmark (DTU).

“If you develop an antibody that binds to the antigen, then these complexes of antibody and antigens can accumulate. So, we need to develop an antibody that not only binds to the antigen but also breaks it down,” explains Ida Marie Boi Jacobsen.

She is particularly focused on the effect on bones. Worldwide, one in three women over the age of 50 is affected by osteoporosis.

“Our primary hope is that it helps prevent bone loss. That’s where we have the strongest data. But we also believe it can prevent obesity and overall metabolic decline. And we’re hopeful the antibody may also help with hot flashes. That’s just extremely hard to demonstrate in mice.”

Mice do not naturally go through menopause, so their ovaries are removed to create a model for menopause. With the Frontier Grant, the researchers can now carry out long-term mouse studies, where they will examine, among other things, the effects of LH on bones, weight, and fat deposits.

Women to participate in trials

Clinical trials are also planned. Over the course of eight weeks, a group of women with moderate to severe menopausal symptoms will receive an already approved medication that also lowers LH levels.

This medication is currently used to suppress sex hormones in transgender individuals and in patients undergoing treatment for prostate cancer. It differs from the antibody that Ida Marie Boi Jacobsen aims to develop in that it also affects another hormone that is not relevant for menopausal women. Nevertheless, the medication can be used in the experimental context, where researchers will examine the effect of reducing LH.

The plan is to compare the results with three other groups of women receiving, respectively, oestrogen, testosterone, and a placebo.

Paul Kristjansen, Senior Scientific Director of Frontier Grants, sees great potential in the project:

“As part of Professor Martin Blomberg Jensen’s vibrant research unit, Ida Marie Jacobsen and her team are taking a pioneering approach to problems related to women’s menopause,” he says.

“Their novel approach may offer an attractive way to alleviate complications such as osteoporosis, hot flashes, and impaired metabolic health. There is a huge unmet need among the many women, whose lives are negatively affected during menopause, and we are excited to be part of the next stages of the project as it progresses from the lab toward clinical proof-of-concept.”

In addition to developing a new drug, Ida Marie Boi Jacobsen hopes the project will also help uncover new knowledge about LH and what happens in the female body when the ovaries are depleted of eggs:

“I think there has been far too little research into menopause. It has been underprioritized for a long time, and I want to help change that”, says Ida Marie Boi Jacobsen.

More about the Lundbeck Foundation Frontier Grant:

Frontier Grants

Frontier Grants facilitate transitions from basic research to attractive prospects for biotech investors