Hormone Replacement Therapy vs Combination Oral Contraceptive for Bone Health in Premature Ovarian Failure

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Hormone replacement therapy improved bone mineral density more than a combination oral contraceptive.
Hormone replacement therapy improved bone mineral density more than a combination oral contraceptive.

In women with spontaneous premature ovarian failure, hormone therapy, as compared with a combination oral contraceptive pill, yielded greater improvements in bone mineral density (BMD) at the lumbar spine, according to data published in the Journal of Clinical Endocrinology & Metabolism.

“Estrogen is produced by the ovaries and women with premature ovarian failure have very low estrogen levels,” study researchers wrote. “Arguably the most important effect of this is bone loss, which can ultimately lead to osteoporosis and fractures.”

They noted that 2 therapies containing estrogen and progestin — combined hormone replacement therapy or a combined oral contraceptive pill — are often prescribed in premature ovarian failure to treat menopausal symptoms, prevent bone loss, and promote cardiovascular health. Previous studies have evaluated these treatments, but none have compared hormone replacement therapy with a combined oral contraceptive in women with purely spontaneous premature ovarian failure, according to the researchers.

For this study, the researchers evaluated 59 women aged 18 to 44 with premature ovarian failure. Thirty elected to receive treatment and were randomly assigned to hormone replacement therapy with estradiol 2 mg daily with the addition of levonorgestrel 75 mcg for 12 days per month or a combined oral contraceptive pill, which contained ethinyloestradiol 30 mcg and levonorgestrel 150 mcg taken daily for 21 days followed by a 7-day break. Participants were assessed at 3, 6, 12, 18, and 24 months.

Sixty-one percent of women completed the trial — 52% of the no-treatment group, 60% of the hormone replacement therapy group, and 80% of the combined oral contraceptive group.

Compared with women taking the combined oral contraceptive, those taking hormone replacement therapy experienced significant increases in BMD at the lumbar spine at 2 years (0.05 g/cm2; 95% CI, 0.007-0.092; P=.025). In contrast, women taking the combined oral contraceptive experienced no significant change and those who opted to receive no treatment experienced decreases in BMD at 12 and 24 months, according to the data.

Further, results indicated that bone turnover markers were similarly reduced in the hormone replacement therapy and the combined oral contraceptive groups, whereas they were largely unchanged in the no-treatment group.

“It is clear from our study that choosing to take no treatment in premature ovarian failure causes of a loss of bone density and that either hormone replacement therapy or the combined oral contraceptive pill is preferable to no treatment. This confirms current opinion and recommendation for estrogen treatment in premature ovarian failure,” the researchers wrote. “Our finding of a possible superiority of hormone replacement therapy compared with the combined oral contraceptive pill at the lumbar spine may be surprising given the relatively higher biological potency of ethinyloestradiol compared with estradiol.”

They noted, however, that their study was limited by its small sample size; relatively high dropout rate; and the fact that the no-treatment group was not randomized.

“A larger, longer multicenter trial needs to be undertaken to confirm or refute our findings of a superiority of hormone replacement therapy compared with the combined oral contraceptive pill on lumbar spine bone density in spontaneous premature ovarian failure,” the researchers concluded. “Our study could be used to guide future research, in particular taking into consideration the difficulties of recruitment and retention in this population.”

Disclosures: The researchers report no competing interests.

Reference

  1. Cartwright B, Robinson J, Seed PT, Fogelman I, Rymer J. Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomised controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab. 2016. doi:10.1210/jc.2015-4063.
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