Histamine and PMDD: The Hidden Link Worsening Your Symptoms

Emerging research shows a potential connection between histamine and PMDD in some women, offering new insights into treatment options and symptom relief.

If you struggle with histamine and PMDD, you’re not alone. Many people don’t realize that histamine, a compound involved in allergies and inflammation, can also influence mood, cramps, and other PMDD symptoms. Understanding the connection between histamine and PMDD could be the missing piece in managing your monthly symptoms more effectively.

In this article, we’ll explore how histamine may worsen PMDD symptoms, the role of antihistamines in PMDD treatment, and how targeted supplements—like key vitamins, minerals, herbs, and probiotics—can help balance hormones and ease symptoms naturally.

TL;DR: Histamine and PMDD

• Histamine can worsen PMDD: Estrogen raises histamine while lowering the enzyme (DAO) that clears it, amplifying mood swings, headaches, cramps, and inflammation.

• Antihistamines may help: Some women find symptom relief with medications like loratadine or famotidine, but results vary and more research is needed.

• Natural support matters: Quercetin, vitamin C, stinging nettle, probiotics, and stress reduction strategies may help balance histamine and ease PMDD symptoms.

• Lifestyle makes a difference: A nutrient-rich, lower-histamine diet, consistent sleep, and gentle exercise support hormone balance and resilience.

• Targeted supplements can support brain and hormone health: Options like Balance Women’s Hormone Support, Adrenal Support, Women’s Probiotic, and Radiant Mind (saffron, bacopa, citicoline, zinc) provide research-backed nutrients to promote mood, cognition, and overall well-being during the luteal phase.

How Histamine Triggers PMDD Symptoms in the Luteal Phase

Histamine is a neurotransmitter and immune system messenger that helps to manage inflammatory responses (inflammation), digestion, and hormone regulation. 

For those with histamine intolerance¹, the body struggles to break down histamine efficiently, leading to an overload of histamine that can contribute to or worsen PMDD symptoms, as well as symptoms of endometriosis², PMS, and other conditions.

However, you don’t have to have histamine intolerance or mast cell activation syndrome or MCAS (a condition in which your mast cells overact with an allergic response to certain triggers) to have histamine contributing to your PMDD symptoms. 

Histamine and PMDD: Key Ways It Worsens Mood, Cramps, and Inflammation

Women with PMDD often notice that their PMDD symptoms are most pronounced during the luteal phase³ of their cycle. Here's more about the link between histamine and PMDD:

• Estrogen increases histamine levels: During the luteal phase (the week before your period), fluctuating estrogen can trigger higher histamine release, leading to mood swings, headaches, other types of discomfort, and irritability—all of which are common PMDD symptoms. This is especially true when progesterone is not sufficient to challenge the estrogen present.
  
  Here’s how estrogen influences histamine levels:
  
  • Stimulates mast cells to produce more histamine
  • Reduces DAO enzyme activity (the enzyme that clears histamine)

• Histamine and inflammation: Increased histamine contributes to systemic inflammation, which can exacerbate cramps, bloating, and fatigue.

• Histamine amplifies PMS symptoms, too: Symptoms like anxiety, insomnia, and migraines can be intensified when histamine is high, meaning that women without PMDD but who deal with symptoms can also be affected by histamine.

• Histamine promotes more estrogen: Yes, when estrogen elevates histamine, then histamine increases estrogen in a viscous cycle. The current working theory is that estrogen is the primary driver of histamine issues in most cases of PMDD and that elevated histamine then perpetuates rising estrogen levels.

Is Histamine a Hormone or a Neurotransmitter in PMDD?

Histamine is not a hormone—it is a biogenic amine that acts as a neurotransmitter and plays a crucial role in immune response, digestion, and brain function. However, histamine interacts with hormones, particularly estrogen, which can influence its levels and effects in the body, as is the case in PMDD. 

This histamine-hormone connection is why some individuals experience histamine related symptoms during hormonal fluctuations, such as in the luteal phase, around ovulation, in perimenopause, or during fertility treatments. 

Histamine is released by mast cells, basophils, and certain neurons, which is why we can see symptoms like irritability or mood alterations, along with allergic-type symptoms (runny nose, itchy eyes, etc).

Understanding that while histamine is not a hormone, it can both influence hormones and be influenced by them is an important component of addressing PMDD in those who have a histamine sensitivity or histamine intolerance.  

Signs of Histamine Intolerance That Can Worsen PMDD

Wondering if histamine intolerance could be worsening your PMDD symptoms? Look for these common signs⁴:

• Headaches or migraines around your period
• Anxiety, irritability, or mood swings during the luteal phase, especially the 5 to 10 days leading up to your period
• Skin issues signifying sensitivity, like hives or eczema
• Digestive symptoms, such as bloating, diarrhea, or nausea
• Sensitivity to high-histamine foods, including aged cheeses, fermented foods, or wine

If these symptoms resonate with you, there's a chance that reducing histamine levels may help to manage your PMDD symptoms.

Related: Guide to Treating PMDD (Premenstrual Dysphoric Disorder).

Antihistamines for PMDD Relief: What the Research Shows

Antihistamines are not currently the first-line treatments for PMDD and are still being studied. Some research, along with anecdotal evidence, suggests that antihistamines may offer some symptom relief for PMDD⁵ by reducing inflammation and stabilizing moods, although it's still debatable if this approach will work as well as others. 

Which antihistamine for PMDD is best? Based on limited available research, here's an overview of the different types of antihistamines for PMDD⁶:

• Claritin for PMDD (Loratadine): Claritin is a non-drowsy antihistamine that may help manage mood swings, headaches, and bloating in some women with PMDD, often without causing fatigue.

• Famotidine for PMDD: Famotidine is commonly used as a heartburn medication, but it may also block histamine receptors and reduce inflammation and mood disturbances due to its effects on the nervous system⁷.

Generally, a licensed medical provider will put you on a combination of these medications to determine if histamine may be at play and if your symptoms improve. The combination of claritin and famotidine for PMDD usually yields at least some symptom improvement within 3 days of use, if histamine is the issue.

It's important to point out that while antihistamines can help some women, they’re not a one-size-fits-all solution for PMDD, endometriosis, or other conditions such as autism and ADHD in women, which also have a connection to histamine.

If you’re considering an antihistamine for PMDD, talk to your healthcare provider to find the best option for you, which can include combining an antihistamine with other remedies like supplements and diet changes.

Related: 

ADHD and PMDD Hormone Connection

PMDD in Autistic Women: Symptoms, Causes & Effective Solutions

ADHD Types and Hormones: The Unexpected Link You Need to Know

Best Medications for PMDD: Anti-Histamines to Hormonal Options

Aside from antihistamines, other medications can be useful in treating PMDD⁸ by targeting hormonal imbalances, mood disturbances, and physical symptoms. 

The choice of medications that will work best for you depends on the specific symptoms you're experiencing and the severity. All of these medications come with side effects, some of which are more significant based on your health history. It is best to talk to your doctor about what treatment is right for you.

Here are some medications that are used⁹ to manage PMDD:

Antidepressants (SSRIs/SNRIs):

• First-line treatment for mood-related PMDD symptoms.
• Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro) help regulate mood and reduce irritability, anxiety, and depression.
• Can be taken continuously or only during the luteal phase (the two weeks before menstruation).

Hormonal Therapies:

• Oral contraceptives (birth control pills) help stabilize hormone fluctuations and reduce PMDD symptoms.
• Gonadotropin-releasing hormone (GnRH) agonists (like leuprolide) may be used in severe cases to induce temporary menopause and stop ovulation. Need estrogen add back therapy.
• Ulipristal acetate (UPA), also known as Ella, is a selective progesterone receptor modulator (SPRM) that blocks the effects of progesterone in the body. 
• Low dose oral micronized progesterone maintains a steady state of progesterone in the body, which reduces fluctuations and increased allopregnenolone production.

Anxiolytics (Anti-anxiety medications):

• Used short-term for severe anxiety symptoms not fully managed by antidepressants.
• Benzodiazepines (e.g., alprazolam) may be prescribed but are used cautiously due to the risk of dependency.

Pain Killers and Diuretics:

• NSAIDs (like ibuprofen) reduce cramps, pain, and inflammation.
• Diuretics can help relieve bloating, breast tenderness, and water retention by promoting fluid loss. Spironolactone is a commonly used diuretic for PMDD.

Natural Remedies for PMDD and Histamine Balance (Supplements, Diet, Stress)

While many women find relief through painkillers or antidepressants for PMDD (such as SSRIs), others prefer natural approaches that target hormonal imbalances and inflammation. The best approach is one that works for you.

In addition to trying the supplements listed below and medications mentioned above, if you suspect histamine is worsening your PMDD, here are steps you can take to find relief:

1. Adopt a Low-Histamine Diet

Diet plays a major role¹⁰ in managing histamine intolerance and PMDD. Reducing high-histamine foods can help lessen inflammation, stabilize your mood, and leave you feeling overall better.

• Avoid aged and fermented foods like aged cheeses, cured meats, sauerkraut, and soy sauce.
• Limit alcohol consumption, especially red wine and beer, which are high in histamine.
• Reduce intake of added sugar and refined carbohydrates, along with most processed and packaged foods, which often contain hidden histamine-boosting additives.
• Incorporate fresh fruits and vegetables like apples, broccoli, and leafy greens, which are naturally low in histamine.
• Support detox pathways with cruciferous vegetables (broccoli, cauliflower) that aid in estrogen metabolism.

A strict, low histamine diet is not going to work for everyone and if you struggle with stress, food anxiety, or an eating disorder then the downsides of this approach likely outweigh the benefits.

2. Try Natural Antihistamines

Certain natural compounds, found in both foods and supplements, can often help reduce histamine levels and may be helpful for managing PMDD symptoms:

• Quercetin: A natural antihistamine that can help stabilize mast cells and reduce histamine release¹¹. It's found in:
  • Apples (especially with skin)
  • Red onions
  • Capers
  • Berries (blueberries, cranberries)
  • Kale and spinach
  • Broccoli
  • Green tea

• Vitamin C: Supports histamine breakdown¹² (making it useful for allergies, too) and acts as a powerful antioxidant. It's found in:
  • Citrus fruits (oranges, lemons, grapefruits)
  • Bell peppers (especially red and yellow)
  • Strawberries
  • Kiwi
  • Broccoli
  • Brussels sprouts
  • Papaya

• Stinging Nettle: Helps reduce histamine production¹³ and supports immune health. It's found in:
  • Herbal teas made from dried nettle leaves
  • Nettle supplements (capsules or tinctures)
  • Fresh nettle (cooked like spinach—be sure to cook or dry it to neutralize the sting)

3. Try Saffron for Mood Relief 

In one randomized controlled trial published in Advanced Biomedical Research¹⁴ saffron was evaluated as a treatment for premenstrual dysphoric disorder (PMDD). In this study, 120 women with PMDD were assigned to receive either fluoxetine (20 mg twice daily), saffron (15 mg twice daily), or placebo during the luteal phase for two menstrual cycles. Results showed that saffron significantly improved PMDD symptoms compared to placebo based on the Daily Record of Severity of Problems (DRSP), and its effects were comparable to fluoxetine, one of the most commonly prescribed SSRIs. 

Importantly, saffron produced fewer side effects than fluoxetine, suggesting it may be an effective and better-tolerated alternative for some women. The total dose recommended based on this study is 30 mg daily. But keep in mind that supplements are not meant to be a replacement for medication, so always talk with your provider about what is best for you. 

Saffron at a dose of 30 mg daily has also been shown to reduce the severity of PMS symptoms¹⁵.

Many women notice that symptoms like mood changes, brain fog, or increased stress sensitivity feel more pronounced during the luteal phase of their cycle. These experiences may be influenced by shifts in hormones, histamine levels, and neurotransmitter activity. Supporting your brain and body during this time can make a meaningful difference in how you feel.

Radiant Mind was formulated to provide gentle, research-backed support for women navigating hormonal changes. It combines four carefully selected nutrients that work together to nourish the brain and promote resilience:

• Affron® Saffron Extract (30 mg): Traditionally used for emotional well-being and studied for its role in supporting a positive outlook.

• Bacognize® Bacopa (300 mg): An adaptogenic herb that helps the body adapt to stress and supports healthy cognitive function.

• Cognizin® Citicoline (250 mg): Provides nutritional support for brain energy and focus.

• Zinc (10 mg): An essential mineral that plays a key role in neurotransmitter balance and hormone health.

Radiant Mind is made with standardized, clinically studied ingredients and is third-party tested for quality and purity. While not intended to diagnose or treat any condition, it can be a supportive part of a lifestyle that prioritizes brain health, emotional balance, and overall vitality during times of hormonal fluctuation.

4. Support Gut Health

A healthy gut is key for managing both histamine intolerance and hormone balance due to the gut-brain connection as well as the impact of the gut on hormones¹⁶. Since histamine is broken down in the gut, improving gut health can often help manage PMDD symptoms.

• Take a high-quality probiotic (like the Women’s Probiotic) to balance gut bacteria and reduce histamine production.
• Eat probiotic foods like yogurt, kefir, and kombucha.
• Incorporate prebiotic-rich foods into your diet, like garlic, onions, and asparagus, to feed beneficial bacteria.
• Include magnesium-rich foods (spinach, pumpkin seeds, almonds) to help regulate estrogen metabolism.
• Incorporate omega-3 fatty acids from wild-caught fish, chia seeds, and flaxseeds to reduce inflammation.
• Avoid gut irritants like artificial sweeteners, processed foods, and high-sugar diets.

Try Women’s Probiotic:

• Supports a healthy gut¹⁷ and estrobolome (the gut bacteria that regulate estrogen metabolism).
• Aids in bloating, supports clear skin, and promotes a balanced vaginal microbiome.
• Supports your innate system to break down histamine¹⁸, reducing the inflammatory load during your cycle.

5. Support Ovarian Hormones

Supporting your body in making estrogen and clearing it when it is no longer needed can be a key factor that aids in reducing PMDD symptoms. In addition, keeping progesterone levels at a steady state, instead of swinging high, then low, can also be of benefit.

My Dr. Brighten Essentials Balance Women’s Hormone Support supplement can help you in these areas. But you don’t have to use my supplements—you can simply take a look at what can be helpful in them:

Try Balance Women's Hormones Support:

• Chaste tree extract (Vitex) can help balance estrogen and progesterone¹⁹ and can often aid the body in PMS or PMDD²⁰ symptoms.
• DIM, sulforaphane, and Calcium-D-glucarate aid in estrogen elimination through the liver and gut the. Designed to help your body’s own detox system work at it’s best.
• Resveratrol and broccoli seed extract provide antioxidant support, reducing inflammation.
• B vitamins²¹, including B6 and B12, plus folate, magnesium, and calcium²² to help support mood, hormone balance, and overall menstrual health²³.

6. Focus on Stress Reduction

Chronic stress can elevate histamine levels and often worsens sleep quality, pain, and PMDD symptoms. Implementing stress management strategies is one smart way to help rebalance hormones and reduce inflammation.

• Practice mindfulness techniques like yoga, deep breathing, or meditation.
• Incorporate adaptogenic herbs (found in Adrenal Support) to help regulate cortisol levels.
• Get regular exercise—since gentle movement like walking, Pilates, or swimming can help naturally lower stress hormones.
• Prioritize sleep, aiming for 7-9 hours per night to support hormone balance.

Try Adrenal Support:

• Contains adaptogenic herbs like Rhodiola and Ashwagandha to help support healthy levels of cortisol²⁴ and reduce stress.
• Supports the HPTA axis (hypothalamic-pituitary-adrenal) for balanced hormone production.
• Promotes healthy levels of dopamine, norepinephrine, and epinephrine to stabilize mood.

Comparison of PMDD and Histamine Treatment Options & Supportive Therapies 

The following is a list of options and supportive therapies to discuss with your provider. 

Treatment Option	How It Helps	Limitations / Considerations	Best For
SSRIs/SNRIs (e.g., Prozac, Zoloft, Lexapro)	Regulate serotonin, reduce anxiety, irritability, depression	Possible side effects (weight gain, sexual dysfunction, nausea)	Moderate to severe mood-related PMDD
Hormonal Therapies (oral contraceptives, GnRH agonists, progesterone, UPA)	Stabilize hormones, reduce ovulation-related PMDD symptoms	Side effects, not suitable for all, some induce temporary menopause	Severe PMDD or when first-line treatments fail
Anxiolytics (benzodiazepines)	Short-term relief for severe anxiety	Risk of dependency, sedating	Short-term use in extreme anxiety cases
Pain Killers (NSAIDs like ibuprofen)	Reduce cramps, inflammation, pain	May cause GI irritation with long-term use	Women with cramps and pelvic pain
Diuretics (spironolactone)	Reduce bloating, water retention, breast tenderness	Can alter potassium levels, requires monitoring	PMDD with significant bloating and swelling
Antihistamines (loratadine, famotidine)	Block histamine receptors, may reduce mood swings, headaches, inflammation	Limited research, variable response, not first-line	PMDD symptoms worsened by histamine
Low-Histamine Diet	Reduces histamine load from food triggers	Restrictive, not sustainable long-term	Women who notice flares with wine, cheese, fermented foods
Natural Antihistamines (quercetin, vitamin C, stinging nettle)	Stabilize mast cells, support histamine breakdown, reduce inflammation	Effects are milder than pharmaceuticals	Women seeking natural support for histamine sensitivity
Stress Reduction (yoga, meditation, adaptogens in Adrenal Support)	Reduces cortisol and histamine, improves mood stability	Requires consistency; adaptogens take weeks to show effect	Women whose mood flares are worsened by stress and poor sleep
Adrenal Support (Dr. Brighten Essentials)	Contains rhodiola + ashwagandha to regulate cortisol, balance stress response	Not a direct PMDD treatment; supportive	Stress-driven hormone symptoms, fatigue
Gut Health Support (probiotics, prebiotics, omega-3s, magnesium)	Improves estrogen metabolism, reduces inflammation, aids histamine breakdown	Requires ongoing use for benefits	Women with bloating, gut issues, or skin flares tied to cycle
Women’s Probiotic (Dr. Brighten Essentials)	Supports gut and vaginal microbiome, aids estrogen/histamine metabolism	Must be taken consistently for effect	Women with histamine intolerance, bloating, acne, vaginal imbalance
Balance Women’s Hormone Support (Dr. Brighten Essentials)	DIM, sulforaphane, resveratrol, vitex, B vitamins — supports estrogen detox, hormone balance, and luteal phase stability	Not an instant fix; works gradually	Women with hormone-driven mood and physical symptoms
Radiant Mind (Dr. Brighten Essentials)	Combines saffron (mood, resilience), bacopa (cognition, stress), citicoline (brain energy), zinc (hormone + neurotransmitter support)	Not a direct antihistamine; brain-focused	Women with experiencing low mood, mood swings, brain fog, or anxious thoughts
Lifestyle (exercise, sleep hygiene, mindfulness)	Improves mood, reduces stress, stabilizes hormones	Benefits lost if inconsistent	Foundational for all women with PMDD
Cognitive Behavioral Therapy (CBT)	Evidence-based talk therapy that reduces anxiety, depression, and emotional reactivity in PMDD	Requires time, access to trained therapist, commitment to sessions	Women seeking non-drug, long-term strategies for mood and coping

Frequently Asked Questions About Histamine and PMDD

Final Thoughts on Managing Histamine and PMDD Naturally

• The relationship between histamine and PMDD is an example of how complex hormonal health truly is. 
• If you’re struggling with severe PMS or PMDD and suspect histamine could be part of the problem, small changes—like adjusting your diet, adding targeted supplements, or exploring antihistamines for PMDD—can make a significant difference.
• Remember, there’s no one-size-fits-all solution for PMDD, but understanding your body’s unique needs is a powerful first step toward finding relief.

BACOGNIZE® is a registered trademark of Verdure Sciences, Inc.
Cognizin® is a registered trademark of KYOWA HAKKO BIO CO., LTD.
Affron® is a registered trademark of Pharmactive Biotech Products, S.L.U.

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