Cynthia Stuenkel, MD, reviews diagnosis, management, and fertility considerations in women with primary ovarian insufficiency.
At the 2025 Menopause Society Annual Meeting, Cynthia A. Stuenkel, MD, MSCP, discussed the evaluation and management of primary ovarian insufficiency (POI), emphasizing the importance of timely diagnosis, hormone therapy, and individualized counseling for affected patients.1,2
According to Stuenkel, the diagnosis of POI is confirmed when a woman younger than 40 years stops having menstrual cycles, her follicle-stimulating hormone (FSH) level is elevated, and her estradiol level is low. “We might have even repeated that just to be sure,” she noted. Once POI is established, clinicians aim to identify potential underlying causes, although “we often can’t establish the cause, but sometimes we can.”
Stuenkel recommended chromosome analysis to assess for Turner syndrome mosaics. “Most Turner’s girls will have primary amenorrhea and won’t go through puberty on their own, but if they have the mosaic, then they can have menarche, have natural cycles, and then go on to have primary ovarian insufficiency,” she said. She also highlighted testing for the fragile X premutation, which “in women…about one in five of those will go on to have primary ovarian insufficiency.” Identifying this mutation warrants genetic and family counseling.
Autoimmune etiologies are another consideration. Stuenkel advised evaluating for adrenal antibodies, particularly 21-hydroxylase antibodies, as positive results may indicate the need for adrenal function testing given the risk of Addison's disease. She also recommended assessing thyroid function and looking for clinical clues, such as alopecia or skin changes, that might signal a broader autoimmune syndrome.
Hormone therapy (HT) remains the cornerstone of POI management. “In general, we like to start it right away at the time of the diagnosis,” Stuenkel said. For younger women, oral contraceptives may be an acceptable and familiar option, particularly if contraception is also desired. In older postmenopausal women, lower doses are typically used. “We use a much lower dose in a postmenopausal woman…we would start at a lower dose than a young woman with POI,” she explained.
Stuenkel emphasized that therapy should continue until the average age of natural menopause, about 50 to 51 years. Beyond that, decisions should be individualized based on patient preference and comorbidities, such as cardiovascular risk factors or a history of estrogen-sensitive cancers.
Fertility can be challenging for women with POI, but Stuenkel encouraged referral to reproductive specialists. “It’s not likely, but it’s possible that she can conceive,” she said. Evaluation may include measuring anti-Müllerian hormone and performing antral follicle counts. Alternatives such as adoption, surrogacy, or egg or embryo donation should also be discussed.
Bone health is a major concern for these patients, who may not have achieved peak bone density before estrogen loss. “The estrogen we give to her will help her not lose any more bone and potentially build her bone,” Stuenkel stated. She advised against long-term use of osteoporosis drugs in this younger population due to safety concerns and potential pregnancy.
Cardiovascular health should also be prioritized. “We have some evidence that taking estrogen for these young women can help promote cardiovascular health,” she noted. Lifestyle counseling is essential, including recommendations to avoid smoking, limit alcohol intake, maintain a healthy weight, exercise, and ensure adequate calcium and vitamin D intake. She referenced the “Life’s Essential 8” framework, emphasizing diet, exercise, glucose and lipid control, blood pressure monitoring, and sleep quality.
Stuenkel also discussed fertility preservation strategies, particularly for women undergoing cancer therapy. “They can either have a part of their ovary removed and put on ice, or go through an ovarian stimulation…harvest their eggs, [and] put those on ice,” she said. Advances in oncofertility, such as ovarian tissue cryopreservation, provide new opportunities for reproductive planning. “If they can get some of their ovarian tissue or eggs on ice, I think that’s peace of mind, and that’s a good thing that they can do for their future fertility,” she concluded.
Stuenkel reports no relevant disclosures.
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