Contraceptives Found As Effective As Traditional Hormone Therapy for POI Bone Loss

With Amanda Vincent PhD and Stephanie Faubion MD

Women who experience premature ovarian insufficiency (POI) suffer the same symptoms as women in menopause, including:

• vaginal dryness

• hot flashes

• disrupted sleep

• loss of fertility

• an increased risk of depression, dementia, and Parkinson’s disease

• reduced bone mineral density (BMD), especially in the lumbar spine

The usual treatment is long-term hormone replacement therapy, using estradiol (E2) and conjugated estrogens (CEs). Synthetic estrogen that is found in continuous oral contraceptives (COC) has also been used to treat women with POI. While researchers have looked at how those compounds impact women who have normal ovarian function, there has been no study looking at the impact on bone mass in those with POI until now.

This new study observed 119 women who had been diagnosed with POI before the age of 40. The researchers looked at 420 bone scans this group had for lumbar spine, femoral neck, and total femur bone mass measurements. The women were divided into groups based on the type of therapy they used: those on contraceptives, and those on a low-dose estrogen/progestin combination with medroxyprogesterone acetate or 1 mg E2 used with norethisterone (a high-dose estrogen/progestin combination), or tibolone. Additionally, there was a control group of women not using any therapy.

Those taking oral contraceptives registered an increase in bone mass at the lumbar spine and total femur, as did those on high dose hormone therapy. In the latter group, though, the effect was not as strong. For the other groups, including the untreated group, there was a loss of bone mass in the lumbar spine. All groups experienced a decrease in bone mass at the neck of the femur. Only the low dose hormone therapy group saw a loss of bone mass in the total femur.

The authors noted that femur bones take longer to show improvement than lumbar spine and femur neck, which may account for the lack of improvement in that area for all groups. Over a period greater than two years, there may be different results.

“The study provides useful information related to the continuous use of the COC as a method of hormone replacement for women with POI and bone health issues,” says Amanda Vincent, Ph.D., head of early menopause research at Monash University in Victoria, Australia.

Among the strengths of the study are that all of the patients had uniformity in bone density testing, says Stephanie Faubion, MD, the medical director of the North American Menopause Society and Director of the Mayo Clinic Center for Women’s Health. “Another strength is that they examined more than one type of menopausal hormone therapy, as well as different doses with a 30- mcg oral contraceptive pill. Also, the oral contraceptive was taken continuously, eliminating gaps in estrogen use.”

Vincent notes that in some previous studies in which women have used oral contraceptives as normal – three weeks of pills with active hormones and one of inactive – add up to 12 weeks without any estrogen. In comparison with hormone therapy with estradiol, some of this research has shown that there is less benefit to bone density in oral contraceptives used for POI. “This decreased response may be due to the type of estrogen, ethinyl estrogen, used in the COC, but may also be due to the long duration without any estrogen,” she says.

The results aren’t surprising, says Vincent, and are consistent with both previous data and current guidelines that women with POI should get estrogen therapy to prevent bone loss. Faubion notes that similar results have been found in women with anorexia who experience bone loss.

Some younger women who have experienced POI don’t want to use medications made for menopausal women, but would rather take something more “peer friendly,” Vincent says. “This can help us in our discussions with women about hormone therapy options for them. Also, for women with spontaneous POI, there exists a very small chance of pregnancy, so that women who do not wish to become pregnant need to use some form of contraception. This study provides evidence that COC can provide both bone health benefits and contraception simultaneously if needed.” Regular hormone therapy does not act as a contraceptive.

That said, Vincent notes that there is no evidence in this study that patients or providers should change from hormone therapy to continuous contraception. “It does provide reassurance that its use is a reasonable option for women who choose it.” She would like to see a larger trial to confirm the findings in the future.

Faubion also notes that the sample was a “convenience sample,” and that it was carried out over a relatively short period of time. Like Vincent, she wants a randomized controlled study to confirm the results.

Vincent also notes that any hormone therapy should be individualized to patient preferences, the need for contraception, and other health issues. “You would not use the COC in a woman who has an increased risk of deep vein thrombosis, or stroke – for example for someone who is over 35, obese, and/or a smoker – or who is hypertensive,” she says.

“No one is, or should be, suggesting that COC is superior to hormone therapy for maintenance of bone density in this population,” Faubion says. “The bulk of the data do not support that notion. Indeed, this study confirmed that physiologic dosing – high dose –of menopausal HT regimens was effective in maintaining bone mass.” What it did affirm was the consensus of multiple recommendations to aim for higher doses to maintain bone – and potentially brain and heart health – in women with POI and premature menopause.

Faubion adds that COC contains the equivalent of 3-4 times the dose of hormone that menopausal hormone therapy contains, depending on the doses used. “Most women don’t need a supraphysiologic dose of hormones though, which comes with greater risks, strokes being one of them.”

This is for women who do not want to get pregnant. Most other women should use physiologic dosing for premenopausal women – what is referred to as high dosing in this paper.

What is important from this is the evidence that there are choices, says Vincent. “I’m pleased to have evidence that continuous use of oral contraceptives was associated with an increase or stable bone density, and is therefore a suitable hormone therapy option with POI.”