PMS and PMDD

What are Premenstrual Syndrome and Premenstrual Dysphoric Disorder?

50-80% of women struggle with challenging physical and mood symptoms in the second half of their cycle, called the luteal phase. This is at the peak cumulative levels of estrogen and progesterone that occur after ovulation and before menses. These conditions are called premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). PMDD is the most severe form of PMS, with up to 8% of women experiencing severe PMDD symptoms.

These symptoms can significantly impair functioning and include:

• Mood symptoms: depression, irritability, and anxiety
• Physical symptoms: breast pain, bloating and swelling
• Pain: headaches and heightened pain sensitivity

Symptoms must be absent outside of the luteal phase, meaning women must be symptom-free during the follicular phase. If a woman experiences symptoms in the follicular phase, a diagnosis of dysthymic disorder or major depressive disorder. These other conditions may worsen during the luteal phase but can have different treatment options. You can learn more about PMS and PMDD in our in-depth article.

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Traditional PMS and PMDD Treatment Options

Unfortunately, many women don't find relief with traditional treatments for PMS or PMDD. Furthermore, many of these medications, especially antidepressants, have side effects:

1. Antidepressants, such as SSRIs during the luteal phase
2. Ovulation suppressors: estrogen-progestin oral contraceptives, gonadotropin-releasing hormone (GnRH) agonists
3. Anti-anxiety medications: alprazolam (Xanax)
4. Calcium (1200mg/day)
5. Acupuncture
6. Pyridoxine (vitamin B6)
7. Exercise
8. Myo-inositol (2gm of powder)
9. Vitex agnus castus
10. Surgery to remove the ovaries (surgical menopause, used as a "last resort")

Notably, there is a considerably high placebo response, as well, which some women innapropriately get gaslit for.

IV Ketamine for Premenstrual Syndrome and Premenstrual Dysphoric Disorder

Rapid-acting antidepressants are believed to provide relief to PMS and PMDD, such as with allopregnanolone and ketamine. Ketamine has numerous possible beneficial aspects compared to traditional prescription medications:

• Temporary estrogen receptor (ERα) activation, instead of continuous use hormonal contraceptives
  • ERα is the key "anti-neuro-inflammatory" receptor through which estradiol provides anti-inflammatory effects and reduces free radical damage
• Neurotransmitter rebalancing to offset estrogen's effects on glutamate signaling
  • Ketamine's glutamate rebalancing provides its rapid acting effects
• Ketamine's anti-inflammatory effects to counter underlying inflammation in PMS and PMDD
• Global improvements in mood outside the luteal phase
• Pain relief from cramping
• Minimal side effects
• Possible neurocognitive improvements throughout the cycle

While clinical experience of ketamine with PMS and PMDD is promising, formal research is also underway with the FDA. IV Ketamine specifically is the fastest acting form of ketamine therapy, allowing the safest and most effective option for women struggling with mood disorders, especially PMS and PMDD.

IV NAD+ and NR Therapy for Mood in PMS and PMDD

NAD+ is a crucial coenzyme involved in healthy mitochondrial function and energy production. Fluctuations in energy and mood are common in those with PMS and PMDD. NAD+ and NR can help these symptoms in many ways:

• Improved energy and reduced fatigue
• Modulating neurotransmitters such as serotonin and dopamine, which are often dysregulated during the luteal phase
• Reducing oxidative stress
• Cellular repair and anti-inflammatory processes
• Headache reduction

By enhancing cellular resilience and neurochemical balance, NAD⁺ can help stabilize mood, reduce fatigue, and alleviate brain fog—key components of PMS and PMDD. Direct IV delivery of NAD+ allows for optimal absorption, bypassing the digestive system and providing the most efficient and rapid delivery of these beneficial effects.

IV Anti-Oxidants, Amino Acids, Vitamins and Minerals

Multiple studies have demonstrated improvements in PMS and PMDD symptoms in women supplementing their diet with key vitamins and minerals. These are highly dose-dependent effects, however, requiring specific dose and forms to ensure absorption and effect. Doctors at Clarus Health use various IVs as part of a holistic PMS and PMDD treatment plan, including:

• Specific B-vitamins: critical for neurotransmitter synthesis and serotonin/dopamine regulation
  • Your provider must be aware of your health history to avoid vitamin B toxicities
• Magnesium: benefits include reduced fluid retention, cramping, breast tenderness, and mood swings
  • Magnesium doses need to be personalized to your health conditions
• Calcium: necessary for neuromuscular functioning with reductions in anxiety, depression, and bloating
  • Calcium doses need to be adjusted to your dietary intake of calcium to avoid side effects
• Taurine: enhances GABA transmission to overcome dysregulated GABA signaling, especially in PMDD
• Glutathione: powerful anti-oxidant to reduce the inflammatory and oxidative burden of PMS and PMDD

IV infusions bypass the gastrointestinal tract to provide 100% bioavailability for faster and more reliable blood levels. This is particularly valuable for patients with malabsorption issues, chronic stress, or fluctuating hormone levels that may impair nutrient uptake.

Hormone Replacement Therapy

Hormone Replacement Therapy (HRT), particularly with bioidentical progesterone, is an emerging option for women with moderate to severe PMS and PMDD who do not respond well to conventional treatments. Bioidentical hormones are chemically identical to the body’s own hormones and tend to offer a gentler alternative with fewer side effects. Progesterone, in particular, has calming, anxiolytic effects by modulating GABA receptors in the brain—making it especially relevant for the mood disturbances, anxiety, and sleep issues that often characterize PMS and PMDD.

Progesterone replacement is often key to cycle related anxiety and poor sleep

Unlike synthetic progestins found in many oral contraceptives, bioidentical progesterone (e.g., prescription micronized progesterone) may be better tolerated and less likely to cause adverse mood effects. Luteal phase supplementation of natural progesterone can balance progesterone:estrogen ratios and relieve PMS-related irritability and insomnia, and blunt the hormonal fluctuations that exacerbate PMDD symptoms. HRT should be personalized based on hormonal testing during the luteal phase and monitored closely by doctors with expertise in hormone therapy.

Genomics Testing for PMS and PMDD

Certain women have a genetic predisposition to greater sensitivity to hormonal fluctuations. This may influence the risk of developing PMS and PMDD. Several genes appear to influence the risk of these susceptibilities, including variations in:

• Estrogen receptor α
• GABA-A receptor (a mutation shared with schizophrenia)
• Serotonin 1A receptor (HTR1A)
• Brain-derived neurotrophic growth factor (BDNF) with additional epigenetic factors

These varied genes highlight that PMDD is not simply a hormonal disorder but also a neurobiological one, shaped by individual genetic profiles that affect mood, neurotransmission, and hormonal responsiveness. Based on an individual's genetic makeup, a treatment plan can be personalized to sources of their PMS and PMDD symptoms.

Holistic PMS and PMDD Treatment: What to Expect

Dr. Kaveh’s holistic approach to treating the root causes of PMS and PMDD includes the following 3 steps:

1. Preparation: Consultation with Dr. Kaveh to learn about your specific PMS and PMDD patterns to develop a personalized treatment plan
2. Treatment: Most patients undergo IV Ketamine and NAD treatment as a foundation for the management of PMS and PMDD, all under the supervision of Drs. Kaveh and Shrestha
3. Maintenance: Positive effects are sustained through a combination of IV interventions followed by oral supplements and lifestyle interventions, informed by genetic and hormonal testing

Contact Clarus Health with any questions about how HRT and IV Ketamine, NAD+ and antioxidant therapies can help treat the root causes of PMS and PMDD.