Menopausal hormone therapy (MHT) can be just as effective for preventing postmenopausal fracture as bone-specific medications—minus some of the risks.

Rodney Baber AM, Professor of Obstetrics and Gynaecology at the University of Sydney, explains how it works, its potential pros and cons, and when to instigate treatment.

Declining estrogen implicated in bone density loss

Poor bone health is a major health issue in Australia, with approximately 7.5 million people having either osteoporosis or low bone mineral density, Professor Baber says.

After the age of 50, one in three women will experience an osteoporotic fracture, he adds, compared to one in five men.

“There is a sudden drop of bone density in women at the time of the menopause when estrogen levels decline,” he says. “We know that when estrogen is lost early, bone loss occurs quicker, and if menopause comes later, bone is preserved.

“So estrogen is clearly implicated in the bone loss process.”

How menopause hormone therapy helps prevent bone loss

Estrogen has several effects on bone, predominantly acting as an anti-resorptive agent, Professor Baber explains. It induces osteoclast apoptosis, decreases production of a substance that promotes osteoclast differentiation and survival, and regulates T cell action on osteoclasts.

Estrogen also promotes bone formation by reducing osteoblast apoptosis, oxidative stress, and activity of NF-kB (a set of factors that regulate the expression of genes involved in various cellular processes, including in bone).

What works best for fracture prevention: MHT or other agents?

So we know estrogen has bone-preserving effects, but how does treatment with estrogen-containing agents compare to other pharmacotherapies for postmenopausal fracture prevention?

For vertebral fracture prevention, studies have shown results for MHT are very similar to those for other anti-resorptive drugs (bisphosphonates and denosumab), Professor Baber says.

For hip fracture prevention, “hormone therapy, once again, is about as effective as the other anti-resorptive agents,” he says. “The same is true for the risk of fracture at other sites on the skeleton.”

Pros and cons of MHT versus other drug therapies

There are also other factors to consider before choosing what to prescribe.

Bisphosphonates and denosumab are both associated with a risk of atypical femoral fracture and osteonecrosis of the jaw, whereas MHT is not, Professor Baber says.

The absolute risk is small and becomes more significant with long term use.

A drug holiday is possible with bisphosphonates and may be with MHT, he adds. However, it is definitely not possible with denosumab due to the sharp drop in bone mineral density and increase in bone turnover markers that occur following treatment cessation.

Discontinuation of denosumab is also associated with rebound fractures, Professor Baber says.

In contrast, data from the Women’s Health Initiative showed that with four years of follow up, there was no evidence of increased fracture rate following MHT discontinuation, he says.

“In fact, there was a residual benefit for total fractures in women who used conjugated estrogens alone. So that’s a very significant advantage for MHT over denosumab.”

What about breast cancer risk?

Breast cancer and MHT have been conflated and the issue remains an “elephant in the room” for women considering this treatment, Professor Baber says.

A review published in 2022 brings greater clarity about the link between the two.

“What we can say with confidence is that the risk of breast cancer for women using MHT does not increase for less than five years of use. We know the risk of breast cancer is not increased for women who used estrogen alone. We know the risk is not increased for women who choose to use estrogen and body identical progestogens for at least 5 years.”

Moreover, data from the Women’s Health Initiative shows that after five years of using estrogen with a synthetic progestogen, the increased risk equated to as few as eight extra cases per 10,000 women per year, Professor Baber says.

“We also know that with 20 years of follow up, there was no change in breast cancer mortality. And for women who used estrogen alone, risk of death was actually decreased compared to the placebo group.”

Additionally, lifestyle factors like smoking, alcohol intake and exercise play a key role in increasing or mitigating breast cancer risk, Professor Baber adds. “The evidence is clear. If we could take control of our lifestyle and our health … then we wouldn’t have to worry about breast cancer to the extent that we do.”

When should you start MHT for bone health?

Professor Baber stresses that managing bone health is a lifelong process. Strategies like exercise and good nutrition that help build peak bone mass earlier in life remain important in perimenopause and early post menopause, he says. MHT can commence at perimenopause if needed.

He recommends assessing each woman’s bone mineral density in the early postmenopausal phase.

“If it is lower than expected, look for secondary causes of bone loss. But if they’ve been excluded, then MHT will be a very effective treatment which will help to maintain bone density and bone mass and help to reduce the risk of fracture.”

MHT can be continued into later menopause, with IMS Consensus guidelines noting there is no mandatory stopping rule for MHT. If your patient would rather not continue with it, or if contraindications arise, he advises starting either bisphosphonates or denosumab. If patients experience a fracture while on treatment, switch them to one of the anabolic therapies.

Key takeaways:

• MHT helps prevent bone loss and osteoporotic fracture
• MHT prevents, or delays, the need for ‘bone-specific’ medications
• Consider risks and side effects for both continuing and stopping any anti-resorptive therapies
• Preventing bone loss and minimising fracture risk is a lifelong process

Find out more about the actions, effectiveness and side effects of different bone sparing agents in Healthed’s free webcast on Tuesday 5 March. Register here.