Hormone therapy isn’t right for everyone. Some women can’t take it for medical reasons. Some don’t want to. Some have tried it and found it didn’t work for them. And some simply want to know what else exists.
The good news: there are real alternatives. Some are genuinely new—breakthroughs that didn’t exist a few years ago. Others have been around longer but are worth knowing about.
The Breakthrough: NK3 Receptor Antagonists
This is exciting. For the first time, we have medications that treat hot flashes by directly targeting the brain mechanism that causes them—the hyperactive KNDy neurons in the hypothalamus.
These drugs don’t provide estrogen. They don’t affect your hormone levels at all. They simply calm the specific neurons that are misfiring.
Fezolinetant (Veozah)
FDA approved May 2023
- First NK3 receptor antagonist approved for hot flashes
- About 60% reduction in hot flash frequency
- Works directly on the thermoregulatory neurons
- 45mg once daily
- Important: Requires liver enzyme monitoring (check before starting and periodically)
For women who can’t or won’t take hormones but have significant hot flashes, this was the first genuinely new option in decades.
Elinzanetant
**FDA approved December 2024**FDA News Release. FDA Approves Novel Drug to Treat Moderate to Severe Hot Flashes Caused by Menopause. December 2024.- Dual NK1/NK3 receptor antagonist—blocks two pathways
- About 74% reduction in moderate-severe hot flashes by week 12
- May also help sleep and possibly mood (it affects substance P, which is involved in pain and stress)
- Can cause drowsiness—which is a feature if you have insomnia
- Daily dosing
What’s Coming
Cendifensine is in Phase 2 trials. It works on both monoamine and KNDy pathways, and may address mood, food cravings, and hot flashes together. We’ll know more as trials progress.
Antidepressants That Help Hot Flashes
Some antidepressants—SSRIs and SNRIs—reduce hot flash frequency through mechanisms we don’t fully understand. They’re not as effective as estrogen or the NK3 antagonists, but they help some women.
Paroxetine (Brisdelle)
- The only SSRI FDA-approved specifically for hot flashes
- Low dose (7.5mg)—lower than antidepressant doses
- Modest effect—roughly 30-40% reduction in hot flashes
- Side effects can include nausea, headache, sexual dysfunction
- Important: Do not use with tamoxifen (drug interaction)
Venlafaxine (Effexor)
- SNRI used off-label for hot flashes
- Some evidence for effectiveness
- May also help mood symptoms at higher doses
- Can be difficult to stop (discontinuation syndrome)
Other Antidepressants
Escitalopram (Lexapro), citalopram (Celexa), and desvenlafaxine (Pristiq) have some evidence as well. If you’re considering an antidepressant for mood anyway, discussing one with hot flash benefits makes sense.
Other Medications
Gabapentin
- Anticonvulsant used off-label for hot flashes
- Particularly helpful for nighttime symptoms
- May improve sleep as a side benefit
- Side effects: drowsiness, dizziness, weight gain
- Often taken at bedtime
Oxybutynin
- Originally for overactive bladder
- Repurposed for hot flashes (works on sweating)
- Side effects typical of anticholinergics (dry mouth, constipation)
- Sometimes used when other options haven’t worked
Clonidine
- Blood pressure medication
- Modest effect on hot flashes
- Side effects (low blood pressure, drowsiness) limit usefulness for many women
- Not usually a first choice
Ospemifene (Osphena)
- For vaginal symptoms specifically, not hot flashes
- Selective estrogen receptor modulator (SERM)—acts like estrogen on vaginal tissue
- Oral tablet
- Option for women who can’t use vaginal estrogen
- May cause hot flashes as a side effect (ironic, I know)
How to Think About These Options
The NK3 antagonists are the most exciting development for women who can’t or don’t want to take hormones. They work on the actual mechanism causing hot flashes—not just masking symptoms.
Antidepressants make sense when you have both mood symptoms and hot flashes. You might address two problems with one medication.
Gabapentin is worth considering if your hot flashes are worst at night and you’re also struggling with sleep.
For vaginal symptoms, ospemifene or vaginal moisturizers and lubricants are options—though for most women, local vaginal estrogen (which has minimal systemic absorption) is still the most effective treatment.
What NAMS/NCCIH Does NOT Recommend
For completeness, here’s what major medical organizations advise against:
- Custom-compounded “bioidentical” hormones — Quality and consistency issues; not better than FDA-approved bioidentical options
- DHEA supplements (for systemic use) — Limited evidence, unclear safety (though vaginal DHEA is approved for vaginal symptoms)
- Wild yam creams — Your body cannot convert the compounds in wild yam to progesterone
- Kava — Hepatotoxicity (liver damage) risk
None of these options is perfect. All have trade-offs. But having options matters—especially if hormone therapy isn’t right for you.
Discuss these with a provider who understands menopause. What works depends on your specific symptoms, medical history, and preferences.