Reproductive & Maternal Health Resource Center

Reproductive & Maternal Health Resource Center

Disclosures: The authors report no relevant financial disclosures.
June 25, 2020
3 min read

Combined oral contraceptives preserve bone density in primary ovarian insufficiency

Disclosures: The authors report no relevant financial disclosures.
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Women with primary ovarian insufficiency prescribed combined oral contraceptives experienced an increase in bone density at the lumbar spine and total femur compared with similar women prescribed other hormone formulations or no treatment.

Among women with primary ovarian insufficiency (POI), estrogen deficiency is associated with a reduction in bone mineral density (BMD) at an early age, particularly at the lumbar spine, Cristina Laguna Benetti-Pinto, MD, PhD, associate professor in the department of gynecology and obstetrics at the University of Campinas School of Medical Sciences in Brazil, and colleagues wrote in a study published in Menopause.

Osteoporosis spine Adobe
Source: Adobe Stock

“Women with primary ovarian insufficiency should be treated with hormone therapy for long periods to reduce the consequences of hypoestrogenism, including loss of bone mass,” Benetti-Pinto told Healio. “Evidence is lacking comparing the results of different hormonal formulations on bone mass.”

DXA, contraceptive data

In an retrospective, observational study, Benetti-Pinto and colleagues analyzed data from 119 women diagnosed with POI between 2000 and 2016, defined as amenorrhea or menstrual cycles of more than 120 days occurring before age 40 years and at least two follicle-stimulating hormone measurements shown in serum levels of more than 25 IU/L (mean age, 30 years; mean BMI, 24.4 kg/m²). Women were prescribed combined oral contraceptives (30 µg ethinylestradiol plus levonorgestrel, continuously), low-dose HT (0.625 mg continuous conjugated estrogen plus medroxyprogesterone or 1 mg continuous estradiol plus norethisterone), high-dose HT (1.25 mg continuous conjugated estrogen plus medroxyprogesterone or 2 mg continuous estradiol plus 2 mg norethisterone), 2.5 mg tibolone mg, or no treatment. Women underwent DXA scans every 2 years (420 scans). Researchers calculated differences between baseline and final bone mineral density values at the lumbar spine, total femur and femoral neck, and used generalized estimating equations to analyze the effect of treatment over time.

Cristina Laguna Benetti-Pinto

“Changes in BMD were analyzed from the difference between two BMD scans, that is, the difference obtained by subtracting the BMD value obtained at baseline from that obtained at the end of the period for each 2-year interval and for each treatment group, with the results being referred to as deltas,” the researchers wrote.

To evaluate response to the different treatments, researchers analyzed 90 DXA scans (45 deltas) for the continuous combined oral contraceptives group, 184 scans (92 deltas) for the low-dose HT group, 90 scans (45 deltas) for the high-dose HT group, 16 scans (8 deltas) for the tibolone group, and 40 scans (20 deltas) for the group of women not using HT.


Advantages of combined therapy

Researchers observed an increase in bone mass at the lumbar spine and total femur among women treated with a combined oral contraceptives, as well as a “less pronounced” increase in bone mass at the same areas for women prescribed high-dose HT.

At the lumbar spine, there was a loss of BMD among untreated women, in the low-dose HT

group, and among women prescribed tibolone. BMD at the femoral neck decreased in all the treatment groups with the exception of the tibolone group.

“For the total femur, there was a reduction in BMD only in the low-dose HT group,” the researchers wrote.

When researchers compared differences between the two DXA scans, untreated women showed a loss of BMD at the lumbar spine compared with women treated with combined oral contraceptives (P < .001), as did women receiving low-dose HT (P < .001) and tibolone (P = .026).

At the total femur, compared with women who received combined oral contraceptives, untreated women similarly showed a reduction in BMD (P = .014), as did women prescribed low-dose HT (P < .001), and high-dose HT (P = .038).

“Our results showed that continuous use of a combined oral contraceptive can be considered as an option for HT in women with POI,” Benetti-Pinto said. “The formulation containing 30 mg of ethinylestradiol plus 150 mg of levonorgestrel, used continuously, was found to be as effective on bone mass as HT containing estradiol at a dose of 2 mg or conjugated estrogens at a dose of 1.25 mg, also for continuous use, together with progestogens.”

Benetti-Pinto said the findings indicate that combined contraceptives may be part of the therapy for women with POI, respecting the recommendations of WHO eligibility criteria for contraceptive use.

“To provide robust evidence, prospective randomized clinical trials with different HT formulations are needed, evaluating aspects such as adherence, cardiovascular, bone, cognitive and mood responses,” Benetti-Pinto said. “The difficulty in carrying out these studies is the low prevalence of POI, suggesting the need for such studies to be multicenter.”

For more information:

Cristina Laguna Benetti-Pinto, MD, PhD, can be reached at the Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Rua Alexander Fleming 101, CEP 13083-970, Campinas, SO, Brazil; email: