Bone fracture risk for women coming off menopausal hormone replacement therapy (HRT) increases sharply before showing a reduced long-term fracture risk compared with women who never took hormones, new data from a study published in The Lancet indicated.
“It’s reassuring that long term, you didn’t seem to be worse off if you had taken hormones in the past. And it reconfirms that when you first go off the hormones, you’re going to lose some benefit, which can translate into higher fracture risk and that needs attention,” certified menopause specialist Deborah Kwolek, MD, told Medscape Medical News.
“I think this is a good wake-up call that we need to pay more attention to women’s bone health starting at menopause,” said Kwolek, assistant professor at Harvard Medical School in Boston and founding lead of the Mass General Women’s Health and Sex and Gender Medicine Program.
Data on 3 Million Women Included
Researchers, led by Yana Vinogradova, PhD, with the Centre for Academic Primary Care at the University of Nottingham in the United Kingdom, assessed the health records of 648,747 women aged 40 years and older, who were registered with a primary care practice between January 1, 1998, and February 28, 2023, and had a first record for any fracture. These women were matched at the fracture index date with up to five female controls (2,357,125 women) with no fracture history, who were the same age and registered at the same general practice.
Menopausal HRT-related fracture risks were assessed using conditional logistic regression adjusted for demographics, family history, menopausal symptoms, comorbidities, and other medications.
The study was powered to investigate all HRT prescriptions containing estrogen and progestogen in the British National Formulary and to assess risk estimates for up to 25 years after stopping therapy.
Reduced Fracture Risk in Older Age
“Our study suggests that, even after stopping menopausal hormone therapy, women could benefit from notably reduced fracture risk in older age. This likelihood holds for those who might have used menopausal hormone therapy for shorter periods because of concerns such as breast cancer,” the authors wrote.
These results differ in some ways from some previous large studies, including the Women’s Health Initiative post-trial study, which followed 15,187 women for 5 years but found no increased fracture risk after stopping hormone therapy.
Kwolek explained that estrogen has long been known to be important for bone health, especially in the perimenopausal to menopausal transition and estrogen could prevent the bone loss that increases right at menopause. But the general understanding had been that when women go off estrogen the benefits go away.
“We had been saying more recently that when women go off estrogen, there should be a plan for how their bone health may be addressed, potentially with medication and close monitoring,” Kwolek said.
Consider Baseline Fracture Risk
She added that it’s important to consider what a patient’s fracture risk is to start with. For a young, healthy woman who doesn’t have osteoporosis, it’s probably not terribly significant if her risk goes up a bit going off the hormones, Kwolek said, but “for a woman who’s 70 and she comes off her hormones and already has osteoporosis, the effects may be more significant,” Kwolek said. “Maybe at that time you might start another medication to strengthen the bone.”
She cautions against seeing the temporary increase in fracture risk after stopping the hormones as a reason not to start HRT in the first place.
The strengths of this study include its large dataset and long follow-up, Kwolek said. It also calls attention to an area of women’s care that too often is overlooked.
Whether in primary care or gynecologic appointments, she said, “people aren’t paying as much attention to these transitions as I think they should,” Kwolek said.
The authors and Kwolek declared having no relevant financial relationships.