Combined Oral Contraceptives Tied to Increased Bone Mass in Premature Ovarian Insufficiency

By Marilynn Larkin

July 01, 2020

NEW YORK (Reuters Health) - In women with premature ovarian insufficiency (POI), combined oral contraceptives (COCs) use was associated with increased bone mineral density (BMD) compared to low-dose hormone therapy (HT) in an observational study in Brazil.

Dr. Cristina Laguna Benetti-Pinto of University of Campinas, Brazil, told Reuters Health by email, "Although the use of natural estrogens is often recommended, this form of HT does not meet all needs or is not always a treatment with good adherence."

"The literature reports that COC...tends to be seen by women as a simpler and more socially acceptable form of medication," she said. "In addition, combined contraceptives are indicated for women with POI who are still at risk of becoming pregnant and need contraception."

"However," she added, "there is a lack of evidence comparing the results of its use on bone mass, or the available studies have used different regimes than the one we analyzed."

Dr. Benetti-Pinto and colleagues compared the use of COC (continuous 30 mcg ethinylestradiol plus levonorgestrel) with low-dose HT (continuous 0.625 mg conjugated estrogen plus medroxyprogesterone or continuous 1 mg estradiol plus norethisterone); high-dose HT (continuous conjugated estrogen 1.25 mg plus medroxyprogesterone or continuous estradiol 2 mg plus norethisterone); 2.5 mg tibolone; or no treatment.

Bone density scans were performed every year or two. The difference between initial and final BMD values (delta) was calculated for the lumbar spine, total femur, and femoral neck.

As reported in Menopause, 420 scans (210 deltas) from 119 women (mean age, 30) were analyzed. Overall, BMD deltas at the lumbar spine and total femur were greater in the COC and high-dose HT groups.

Women treated with a COC also had increased bone mass at the lumbar spine and total femur. Those treated with high-dose HT showed similar improvements, though less pronounced than in the COC group.

By contrast, there was a loss of BMD at the lumbar spine in the untreated, low-dose HT and tibolone groups. BMD loss at the total femur occurred only in the low-dose HT group, whereas BMD at the femoral neck decreased in all groups except for tibolone.

More specifically, for women using COC continuously for two years, there was a mean increase in BMD at the lumbar spine of 2.5% versus an increase of 1.8% with high-dose HT.

In contrast, there was a BMD loss of - 1.3% with low-dose HT, - 2.2% with tibolone, and - 3.3% with no treatment.

For the total femur, there was a BMD increase of 2.4% with COC compared to increases of 0.9%, 2.2%, and 0.02% for high-dose HT, tibolone, and no treatment, respectively,

Dr. Benetti-Pinto said, "Combined contraceptives are...easily accessible, generally low-cost and, in some countries like ours, Brazil, offered free of charge."

Dr. Richard Leach, Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Biology at Michigan State University in East Lansing agreed. He told Reuters Health he uses COCs for POI. "COCs are well tolerated with a low risk of complications," he said by email. "A prospective clinical trial should be conducted in the US to confirm these findings can be reproduced, since these are preliminary findings in Brazil."

Dr. Kecia Gaither, Director of Perinatal Services at NYC Health and Hospitals/Lincoln, commented in an email to Reuters Health, "It is likely that it can be generalizable to the US; COCs are inexpensive and readily available."

"Clearly, women who may consider this treatment would need to have a complete medical /physical exam prior to beginning this type of therapy, primarily to ensure there are no comorbid medical conditions that would prohibit beginning continuous OCP - e.g., a history of thrombotic phenomena."

"Some side effects to consider," she added, "include weight gain, nausea, breast tenderness, and headache."

SOURCE: Menopause, online June 22, 2020.