Gynecologist Kelly Saunders, MD, has been getting questions about perimenopause treatments being advertised across social media from a growing number of patients. Women are unsure where to begin.

“There are a ton of products on the market that may or may not have evidence behind them, so I hear a lot of questions about that,” said Saunders, an associate clinical professor of obstetrics and gynecology at the University of Arizona in Phoenix. Given the unpredictable constellation of symptoms women can experience during the menopause transition it can be hard for patients to decipher what’s real, what they should believe, and what would be right for them, she said.

A wide range of potential perimenopause treatments are being investigated in clinical trials, from rapamycin to delay ovarian aging to hemp-derived cannabinoids for physical and psychological symptoms. Despite the hype around unproven strategies like combining antihistamines, the number of research-backed options is growing. Some new treatments have shown promising results in early clinical trials.

Half to three quarters of women in perimenopause experience vasomotor symptoms such as hot flashes, night sweats, or both. More than half of the women have genitourinary symptoms, such as vaginal dryness or irritation, pain with intercourse, and urinary dysfunction. Other common symptoms include mood changes, such as irritability, decreased libido, and brain fog or difficulty concentrating, Saunders said.

Treatment goals and approaches vary from one patient to another, said Saunders, who also directs the obstetrics and gynecology residency program at Banner University Medicine Women’s Institute in Phoenix. While many women ask if hormone testing can confirm the transition to menopause, “I really care much more about what they’re telling me their experience is,” Saunders said.

Treatments for Hormone Stability

Sudden estrogen surges can trigger unpredictable bleeding during perimenopause. Aging ovaries respond less consistently to signals from the brain, causing erratic periods. That can lead to unintended pregnancy, a risk for up to 77% of women aged 45-50 years, and unnecessary testing for fibroids or uterine precancer, said Karen E. Adams MD, a clinical professor of obstetrics and gynecology at Stanford Medicine, Stanford, California.

“It’s not so much that we want the periods regular. It’s that we want hormone stabilization,” said Adams, who also directs the program in menopause and healthy aging at Stanford. Hormone therapy contains about four times less hormone than birth control pills, so it can’t help regulate periods and may even cause unpredictable bleeding, Adams said. She usually reserves hormone therapy for postmenopausal patients and prescribes birth control pills or an intrauterine device (IUD) for perimenopausal patients.

Progestin-containing IUDs, such as Mirena or Liletta, can help control the menstrual cycle but may not help manage vasomotor or genitourinary symptoms, Adams said. She often adds an estradiol patch or gel; estrogen hormone therapy alone or combined with a progesterone can reduce vasomotor symptoms by about 75%.

Testosterone replacement therapies have been shown to increase libido in postmenopausal women. Anecdotally, testosterone therapies can also lift brain fog and increase energy in perimenopausal women, Saunders said. But due to a lack of long-term safety information and cardiovascular risk concerns, there are no FDA-approved testosterone therapies for women, “so it’s all off-label use,” Saunders said.

Hormone therapy can help address depression and anxiety in perimenopause, but it’s not considered first-line treatment for those conditions, said Ruta Nonacs, MD, PhD, a reproductive psychiatrist at the Center for Women’s Mental Health at Massachusetts General Hospital and an instructor in psychiatry at Harvard Medical School, Boston. Hormone therapy can be combined with selective serotonin reuptake inhibitors, which “can help with depression and anxiety and also help to reduce vasomotor symptoms,” Nonacs said.

New Treatments

A large-scale 2025 analysis found starting estrogen therapy during perimenopause was associated with a 60% lower risk for breast cancer, heart attack, and stroke compared with starting therapy after menopause or not at all.

Still, many women can’t use hormone-based treatments. Systemic hormone therapy increases the risk for recurrence in women with a history of hormone receptor-positive breast cancer by up to 80%. Women with certain cardiovascular risk factors may also be advised against using hormone therapy.

Estetrol, known as E4, is a natural estrogen that activates some estrogen receptors and blocks others. E4 combined with drospirenone (a synthetic progestin), gained FDA approval as an oral contraceptive in 2021 and may be approved for menopausal therapy this year.

There are pitfalls, however. E4 can cause bleeding between cycles in a third or more of people started on the drug, but the risk decreases over time, Adams said. There is no generic version of E4 and many insurances do not cover it.

Although E4 is a hormone, “It doesn’t have the impact on blood clotting risk and breast tissue that we think birth control pills do,” said Adams.

Neurokinin 3 receptor (NK3R) antagonists are a nonhormonal option for treating vasomotor symptoms. Two NK3Rs are FDA-approved: elinzanetant, a dual-receptor antagonist that blocks the NK1 and NK3 receptors in the brain, and fezolinetant, a selective NK3-only receptor antagonist. NK3R antagonists can cause elevated liver enzymes and may be unsafe for people with liver disease, Adams said. Liver function should be tracked in patients using NK3R antagonists.

“They both hit a part of the brain that is back a step from the hot flash,” Adams said. “They work quickly, and they are as effective as estrogens in managing hot flushes and night sweats and sleep disturbance.” Elinzanetant is especially helpful for sleep, possibly “because it hits an additional receptor in the brain,” she said.

Potential Treatments in the Pipeline

One product gaining momentum for perimenopause treatment is NRPT, a dietary supplement combining the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR) and the antioxidant pterostilbene (PT). NAD+ is a vitamin B3 metabolite that helps produce estradiol, which declines with age. Clinical trials have shown that NRPT may protect from certain effects of ultraviolet B radiation and increase blood NAD+ levels by 40%.

In a pilot clinical trial published this year, NRPT reduced the frequency and magnitude of perimenopause symptoms in 40 healthy women older than 35 years who took a recommended daily dose (250 mg NR and 50 mg PT) for 7 days. The 32 women who self-reported menopausal symptoms before the trial reported significantly reduced bloating, hot flashes, and poor sleep after 7 days. In those women, NRPT also significantly increased urine levels of estradiol and estrone, the main source of estradiol after menopause.

Cendifensine, an investigational drug developed to treat depression, has also shown promise for treating perimenopausal symptoms. A monoamine regulator, it acts on serotonin, norepinephrine, and dopamine, and also affects KNDy neurons (kisspeptin, neurokinin B, and dynorphin), which trigger hot flashes when they get hyperstimulated by drops in estrogen.

In phase 2 trials, cendifensine reduced moderate-to-severe hot flash frequency by 92% and severity by 59% at 12 weeks (the mean baseline number of moderate-to-severe hot flashes per day was 12.7). Symptoms of depression, food cravings, fatigue, and weight gain also improved. Large phase 3 trials are planned.

Supplements and Lifestyle

Saunders said that many patients are interested in supplements for perimenopausal symptoms, sometimes due to mistrust of Western medicine.

Her 2026 research on integrative approaches to perimenopause cites evidence for ashwagandha to improve sleep and help manage stress and anxiety, but the studies are not focused on menopausal or perimenopausal women. Melatonin and magnesium have some evidence for improving sleep, she said, while maca root has been shown in some studies to improve sexual dysfunction (including that induced by antidepressants) in postmenopausal women.

“Some of these can be used together to help someone who may have a constellation of these symptoms,” Saunders said.

Evidence for the effects of exercise on vasomotor symptoms is mixed, but several clinical trials are investigating exercise strategies during perimenopause, including effects on cognitive health, vascular function, and mood when combined with the plant-based supplement sarmentosin-L-theanine.

Even as researchers continue exploring potential treatments, many women’s perimenopause symptoms are being overlooked. Some clinicians may not be aware that symptoms can appear before periods start to change, Adams said.

“On average, women go to five different clinicians before their perimenopausal symptoms get diagnosed and treated,” Adams said. 

At the Menopause Society meeting last year, Adams was pleased to hear discussion around “anticipatory counseling” on perimenopause for women reaching their mid-thirties.

“We should be talking about this,” she said.

The experts cited in this article had no relevant disclosures.