April 16, 2024/Cancer

Watching Out for Primary Ovarian Insufficiency

An underdiagnosed condition in patients with cancer

Women's health physician

Primary (or premature) ovarian insufficiency not only affects a woman’s fertility but puts her health at risk. Unfortunately, it often is undiagnosed, and impacts many women under age 40. This condition often occurs as a result of treatment with certain alkylating and chemotherapy agents and/or radiation therapy at levels above 2-3 Gy (particularly those affecting the brain or pelvis).


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Working on one of the largest interdisciplinary teams specializing in the management of menopause, Pelin Batur, MD, with the Center for Specialized Women’s Health is very familiar with the condition.

“In the medical community, there often isn’t a high degree of suspicion for primary ovarian insufficiency, so it may go unrecognized, but it’s important to identify and treat it,” says Dr. Batur. “Early loss of estrogen before age 40 is associated with many negative outcomes, such as low bone mass, cardiovascular disease, sexual dysfunction and neurological conditions such as dementia and Parkinson's disease.”

Educating patients

When patients are first diagnosed with cancer, they’re understandably facing information overload. But Dr. Batur notes it’s a good idea to have a conversation early on with female patients that treatment may impact their ovaries. This way, the issue is on their radar and they know what to watch for. Likewise, asking patients about their menses during and after treatment should be part of cancer follow-up care. “If a patient is young and their menses have become irregular or stopped, they deserve to have more of a conversation and lab testing to see what’s going on,” Dr. Batur says.

Clinicians should also be aware that spontaneous ovulation occurs in roughly half the cases of primary ovarian insufficiency. In fact, spontaneous rates of pregnancy are 5-10% in these individuals who have been previously told that they have "premature menopause." This is where open dialogue with the patient is essential to explain the potential for pregnancy and to discuss contraceptive options if needed.

What to watch for

If a clinician has a patient who is having irregular menses that have been going on for more than three or four months, checking the following labs is warranted.

  • Follicle-stimulating hormone (FSH) test
  • Thyroid levels
  • Prolactin levels, since this brain hormone can mimic early menopause
  • Estrogen levels (not needed to make a diagnosis, but can support diagnosis)

For patients less than 40 years of age, if their FSH is 25 mIU/mL or greater, there's no thyroid issue or other medical condition to explain loss of estrogen and the patient isn’t taking birth control pills, labs should be checked again a month later. If menses remain irregular and the FSH remains elevated, the patient would be diagnosed with primary ovarian insufficiency. For patients aged 40-45, this would be considered perimenopause or early menopause.

Symptoms can be far ranging. Low estrogen levels are associated with mood changes, insomnia, hair loss, body aches, vaginal dryness, low sex drive, night sweats and trouble concentrating.


In general, if a patient loses estrogen before age 40 and there’s no compelling medical reason not to give it back, it’s advantageous to prescribe hormone replacement therapy. “This should not be confused with typical hormone therapy that's given to women in their 50s and 60s,” explains Dr. Batur. “For women ages 50+, typical menopausal hormone therapy can impact clotting and breast cancer risks with prolonged use. But these risks are not the same for young women who are meant to have high hormone levels naturally, until the natural age of menopause at 52.”


Hormone replacement therapy can be administered systemically via a higher-dose vaginal ring, skin patch, skin gel or oral pill. This treatment can help with symptom management in addition to protecting bone and heart health.

There are a few exceptions to treating with hormone replacement therapy, such as patients who have had estrogen-sensitive cancer. In those cases, non-hormone options need to be considered.

There is a high risk of osteoporosis for those with premature loss of estrogen, so patients should receive baseline and then periodic DXA scans to check bone density.

Primary ovarian insufficiency can also have a widespread mental and physical toll on patients. Bringing together a care team, including hormone specialists as well as those providing psychological support, is beneficial to help improve patients’ quality of life.


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