Evaluating premature ovarian insufficiency


A recent article outlined the risk factors, symptoms, and treatment methods associated with premature ovarian insufficiency.

Evaluating premature ovarian insufficiency | Image Credit: © Alena - © Alena - stock.adobe.com.

Evaluating premature ovarian insufficiency | Image Credit: © Alena - © Alena - stock.adobe.com.

According to a recent article published in the Journal of Clinical Medicine, premature ovarian insufficiency (POI) is associated with risks of increased bone mineral density (BMD), which may cause conditions including osteoporosis, osteopenia, and low energy fractures.

POI presents as ovarian function cessation in women aged under 40 years. Follicle stimulating hormones (FSHs) are evaluated to diagnose POI, with guidelines from the European Society of Human Reproduction and Embryology (ESHRE) stating FSH over 25 IU/L 2 or more times at least 4 weeks apart is indicative of POI.

POI may be caused by chromosomal abnormalities or genetic predisposition. Autoimmune diseases have also been associated with POI, with about 4% to 30% of POI cases being linked to autoimmune conditions. Types of autoimmune origins include adrenal autoimmunity, non-adrenal autoimmunity, and isolated, with adrenal autoimmunity being the most common.

Decreased BMD has been observed in patients with POI. Peak bone mass (PBM), referring to, “the maximum amount of bone tissue present at the end of skeletal maturation,” is often associated with BMD. Early PBM is valuable for bone health, with about 85% to 95% of final mass present in girls aged 18 years and boys aged 20 years.

Factors associated with PBM include race, gender, genetics, physical activity, vitamin D, and health conditions such as rheumatoid arthritis, inflammatory bowel diseases, and anorexia nervosa. Risk factors are measured alongside BMD to determine fracture risks in a patient.

Bone turnover is significantly impacted by estrogen, which decreases osteoclastogenesis and stimulates osteoclast apoptosis. A lack of estrogen receptors alpha (ERα) can cause osteoclast progenitor to increase in the marrow, leading to reduced trabecular bone mass.

Bone cell ERα has been linked to bone adaptation in multiple studies. The number of oxidative stress products in the bone rise with age, decreasing osteoblastogenesis.

The rate of BMD loss in patients with POI has been estimated as 8% to 27%. Women with POI are seen with rates of osteoporosis and fracture risk twice that of the general population, with postmenopausal women having a doubled risk of osteoporosis.

Two main factors have been linked to the association between POI and BMD, the first being reduced PBM accumulation. The second is increased bone remodeling, especially bone resorption, reducing BMD. Bone resorption increases concurrently with estrogen deficiency, making estrogen deficiency duration a vital factor when evaluating risks of BMD loss.

Other risk factors associated with BMD reduction in patients with POI include chemotherapy at a young age, high serum FSH levels, a delay of 1 year or longer in POI diagnosis, low calcium intake, and vitamin D level under 32 ng/mL.

Diagnosing osteopenia and osteoporosis is often more complicated than initially expected. These conditions are most often diagnosed using dual-energy X-ray absorptiometry (DXA) with the ESHRE recommending a DXA be performed in all young patients with amenorrhea for over 6 months.

Limitations from DXA include not being able to distinguish the cortical bone and trabecular bone from each other and not presenting information on bone quality and structure. The cortical bone and trabecular bone can be distinguished using peripheral quantitative computed tomography (pQCT) and high-resolution pQCT, but these methods are expensive and not widely available.

Hormonal replacement therapy (HRT) is recommended for treating premenopausal patients with POI, as HRT leads to improved BMD in the total hip, femoral neck, and lumbar spine. However, it is unclear what the most effective regimen is for HRT.

Treatment recommendations vary between patients, including DXA screening. A follow-up DXA scan of the hip in spine is recommended after 2 years for patients starting therapy. Monitoring can be reduced in patients with stable or improved BMD.

While hormonal options are currently recommended for POI, progress has been made in developing non-hormonal treatments such as intranasal calcitonin, bisphosphonates, raloxifene, risedronate, parathyroid hormones, and strontium ranelate. Investigators recommended further research on non-hormonal treatment options for women with osteoporosis.


Meczekalski B, Niwczyk O, Bala G, Szeliga A. Managing early onset osteoporosis: the impact of premature ovarian insufficiency on bone health. J Clin Med. 2023;12(12):4042. doi:10.3390/jcm12124042

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