In women with spontaneous premature ovarian failure (POF), combined hormone replacement therapy (HRT), as compared with a combination oral contraceptive pill (OCP), 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 POF 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 — HRT or a combined oral contraceptive therapy (COCT) — are often prescribed in POF to treat menopausal symptoms, prevent bone loss, and promote cardiovascular health. 

Previous studies have evaluated these treatments, but none have compared HRT with a COCT in women with purely spontaneous POF, according to the researchers.

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High Yield Data Summary

  • In women with premature ovarian failure, HRT was associated with greater increases in lumbar BMD as compared to combined OCP therapy

For this study, the researchers evaluated 59 women aged 18 to 44 with POF. Thirty elected to receive treatment and were randomly assigned to HRT with estradiol 2 mg daily with the addition of levonorgestrel 75 mcg for 12 days per month or COCT, 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 HRT group, and 80% of the COCT group.

Compared with women taking the COCT those taking HRT 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 COCT 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 HRT and the COCT groups, whereas they were largely unchanged in the no-treatment group.

“It is clear from our study that choosing to take no treatment in POF causes of a loss of bone density and that either HRT or the COCT is preferable to no treatment. This confirms current opinion and recommendation for estrogen treatment in POF,” the researchers wrote. 

“Our finding of a possible superiority of HRT compared with the COCT at the lumbar spine may be surprising given the relatively higher biological potency of ethinyloestradiol compared with estradiol.”

Summary and Clinical Applicability

“A larger, longer multicenter trial needs to be undertaken to confirm or refute our findings of a superiority of HRT compared with the COCT on lumbar spine bone density in spontaneous POF,” 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.”

Limitations and Disclosures

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.

Disclosures: The researchers report no competing interests.

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  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.

This article originally appeared on Endocrinology Advisor