If I skip HRT, what are the biggest health risks (bone, heart)?

The short version: skipping HRT means accepting a real but manageable increase in fracture risk, while the heart risk from skipping is smaller than the heart risk from taking it.

The evidence on bone is clear. Estrogen preserves bone mineral density. The Danish Osteoporosis Prevention Study found that perimenopausal women on HRT gained about 2.2% in BMD over time, while untreated women lost about 6.5% [6]. That is a net difference of nearly 9 percentage points. A separate study showed that high-dose estrogen therapy increased the degree of bone mineralization by about 6.9% compared to before treatment [1]. The WISDOM trial, a randomized placebo-controlled study, found that combined estrogen-progestin reduced osteoporotic fractures by about 31% (HR 0.69), though the result did not reach statistical significance (p=0.07) [4]. The mechanism is straightforward: estrogen slows the bone remodeling cycle, reducing the rate at which osteoclasts break down bone. When estrogen drops at menopause, that brake is released and bone loss accelerates.

The heart picture is the opposite of what most women are told. The WHI and WISDOM trials both found that combined estrogen-progestin therapy increased cardiovascular risk, not reduced it. WISDOM reported a significant increase in cardiovascular events (p=0.016) and a 7-fold increase in venous thromboembolism (HR 7.36) [4]. A separate analysis of WHI data found that the hazard ratio for coronary heart disease in the first two years of combined therapy was 2.36, meaning more than double the risk [2]. The risk did eventually drop after about six years of use, but that is not a cardioprotective profile. Estrogen-only therapy in women without a uterus did not raise heart disease risk in WHI, but it also did not lower it. The idea that HRT protects the heart was based on observational studies that compared users to non-users and got the answer backwards because healthier women chose HRT. The randomized trials corrected that error.

The trade-off is not symmetrical. The bone benefit from HRT is real and measurable. The heart benefit was a myth that randomized trials disproved. If your main concern is bone density, skipping HRT does increase your fracture risk, and that risk can be managed with weight-bearing exercise, adequate protein, vitamin D, and calcium, but those interventions do not match the potency of estrogen for preserving bone. If your main concern is heart disease, skipping HRT is the safer choice, because the therapy itself raises cardiovascular risk, especially in the first years of use.

My call: skipping HRT raises fracture risk moderately and lowers cardiovascular risk compared to taking it. For bone, the loss is real but manageable with non-drug approaches. For heart, skipping is clearly safer. Confidence: moderate.