Menstrual Health: Conditions, Treatments, and Lunapatch Advantages

Science

Sep 27

Written By

Menstrual Health: A group of menstrual conditions emerges in the late luteal phase, commonly referred to as dysmenorrhea, Premenstrual Dysphoric Disorder (PMDD), and Premenstrual Syndrome (PMS). These conditions exhibit varying severity levels during the menstrual cycle, often linked to hormonal fluctuations preceding menstruation. Symptoms result from physiological changes rather than the hormones themselves, suggesting common causes. This article provides an overview of current treatments and introduces Lunapatch as an innovative solution for menstrual pain relief without common side effects found in other options.

Definition and Description of the Symptoms

The World Health Organization's 2016 disease classification characterizes dysmenorrhea as 'a disorder marked by abnormally painful abdominal cramps during menses.' Studies show that dysmenorrhea affects up to 72.7% of women from menarche to menopause (Unsal et al.) [2].

According to the Mayo Clinic:

Premenstrual syndrome (PMS) encompasses various symptoms such as mood swings, tender breasts, food cravings, fatigue, irritability, and depression. It is estimated that up to 75% of menstruating women have experienced some form of PMS.

Symptoms tend to recur in a predictable pattern. But the physical and emotional changes you experience with premenstrual syndrome may vary from just slightly noticeable all the way to intense.

Still, you don't have to let these problems control your life. Treatments and lifestyle adjustments can help you reduce or manage the signs and symptoms of premenstrual syndrome.(Staff, Premenstrual Syndrome (PMS), 2014) [3]

The Mayo Clinic has listed a number of symptoms for PMS:

Emotional and behavioral symptoms:

Tension or anxiety
Depressed mood
Crying spells
Mood swings and irritability or anger
Appetite changes and food cravings
Trouble falling asleep (insomnia)
Social withdrawal
Poor concentration

Physical symptoms:

Joint or muscle pain
Headache
Fatigue
Weight gain related to fluid retention
Abdominal bloating
Breast tenderness
Acne flare-ups
Constipation or diarrhea”(Staff, Premenstrual Syndrome (PMS), 2014) [4]

The Mayo Clinic discriminates between PMDD and PMS as separate conditions, saying:

Premenstrual dysphoric disorder (PMDD) is a severe, sometimes disabling extension of premenstrual syndrome (PMS). Although regular PMS and PMDD both have physical and emotional symptoms, PMDD causes extreme mood shifts that can disrupt your work and damage your relationships. In both PMDD and PMS, symptoms usually begin 7-10 days before menstrual bleeding begins and continues for the first few days of bleeding.

In PMDD, however, at least one of these emotional and behavioral symptoms stands out:

Sadness or hopelessness
Anxiety or tension
Extreme moodiness
Marked irritability or anger (Thielen, 2015) [5]

Treatment of Pain

The most common treatments include over the counter NSAID (Non-steroidal Anti-inflammatory drugs) drugs such as aspirin, ibuprofen, acetaminophen, naproxen as well as other more recent drugs that inhibit the Cox family of enzymes. These drugs have their own downsides. A list of side effects includes:

Serious side effects of these drugs listed by the FDA(U.S. Food and Drug Administration, 2007) [6] include:

• “heart attack

• stroke

• high blood pressure

• heart failure from body swelling (fluid retention)

• kidney problems including kidney failure

• bleeding and ulcers in the stomach and intestine

• low red blood cells (anemia)

• life-threatening skin reactions

• life-threatening allergic reactions

• liver problems including liver failure

• asthma attacks in people who have asthma”

Many of these side effects are already problematic effects of PMS, side effects such as anemia, bleeding ulcers and edema will exacerbate the problems caused by PMS and menstruation.

Treating the symptoms of pain using more potent central nervous system pain relievers such as opiates have a laundry list of side effects. These have been reviewed by Benyamin et. al.

“Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus.”(WebMD, LLC) [7]

Using opiates to treat the pain of PMS has more side effects and dangers than are reasonable for the treatment of premenstrual disorders.

Treatment of Bloating

Diuretics offer a poor option, as this may lead to non-selective depletion of nutrients such as magnesium, which have a renal route of excretion. Products that combine diuretics with NSAIDs have some strong side effects that impair the user’s mental state and alertness.

A list of common side effects of Pamprin Max from Web MD:

“Chronic Trouble Sleeping
Conditions of Excess Stomach Acid Secretion
Feel Like Throwing Up
Heartburn
Irritation of the Stomach or Intestines
Nervous
Stomach Cramps
Throwing Up”(WebMD, LLC) [8]

Treatments for Depression and Mental Distress

Antidepressants are described as a treatment for PMS, but have too broad an effect with too little benefit to be really practical. Antidepressants have become the poster child for the mismanagement of the medical profession’s arsenal of medications. It is common to receive prescription of an antidepressant by the doctor with no plan for eliminating the medication as symptoms are remedied.

In a recent article entitled, “Are Antidepressants Just Placebos with Side Effects?” more evidence unfolds for the poor choice that antidepressants provide.

“After analyzing all the FDA studies, Kirsch concluded that placebos are 82 percent as effective as antidepressants. According to Kirsch, this difference vanishes if antidepressants are compared to "active placebos," which are compounds such as atropine, an alkaloid that blocks certain nerve receptors and causes dry mouth and other symptoms, that have distinct side effects.”

Additionally:

“Although Prozac was touted for its relatively mild side effects, it causes sexual dysfunction in as many as three out of four consumers.”(Horgan, 2011) [9]

With this dizzying number of side effects, how does one relieve the pain and other symptoms of PMS without facing unreasonable risks?

Natural Alternatives to Pharmaceuticals

Magnesium supplementation has shown benefits in alleviating PMS/PMDD symptoms in various studies. A study that claims results 'contrary to prior reports' may mislead women, deterring them from a simple, safe, and effective treatment.

An American study (Khine et al., 2005) [10] concluded:

'Contrary to prior reports, we found no evidence of Mg2+ deficiency in women with PMDD compared with control subjects. Furthermore, Mg2+ was not superior to placebo in the mitigation of mood symptoms in women with PMDD.'

Upon closer examination, there was a trend toward greater magnesium retention in PMDD sufferers, though statistically insignificant. The data did not support the conclusion of 'no evidence of Mg2+ deficiency.

Similarly, participants experienced no worsening of symptoms with magnesium supplementation, and most reported improvement, although statistical significance was not reached in this small group of 17 affected women. The use of 5% glucose as the placebo and carrier for intravenous magnesium may have influenced the results, as glucose is known to be mood-elevating. PMS and sweet cravings often coincide, making 5% glucose a questionable placebo. The study noted that baseline 24-hour urinary magnesium output was below the reference range in both patients and healthy control subjects.

This means that compared to previous studies on magnesium metabolism and retention, both groups (affected and unaffected by PMDD) exhibited very low urinary excretion of magnesium.

After supplementation of magnesium intravenously, an additional difference was noted between groups regarding the amount of magnesium they retained.

“Although the mean of the patients (31.5% retention) exceeded the normal threshold of 27.5%, the mean of the control subjects was exactly at the upper limit of normal (27.5% retention) and did not differ from that of the patients. Thus, our data failed to support the hypothesis that Mg2+ depletion causes PMDD.”

Infusing magnesium at this level resulted in low magnesium excretion for both patients and controls, with some affected individuals showing significantly lower levels. Unfortunately, the study failed to differentiate between those with and without magnesium deficiency, missing the chance to analyze distinct subgroups. The assumption of a single cause for PMDD and an exclusive diagnosis led to a heterogeneous group. Reanalyzing data based on comorbid PMDD and magnesium deficiency could have yielded more meaningful results. In clinical practice, testing PMDD-diagnosed individuals for magnesium deficiency can inform tailored supplementation. While magnesium supplementation may significantly benefit those with both magnesium deficiency and PMDD, the cost/benefit ratio for those without magnesium deficiency is likely low.

The study's methods may lead to limited outcomes, and the conclusions are strongly worded compared to the data. Despite lacking statistical significance, the data generally trend toward a positive effect of magnesium supplementation. The study's failure to subdivide the PMDD group into magnesium-deficient and non-deficient groups makes it seem contrary to previous studies showing long-term magnesium benefits, though the data trends actually support a positive impact on many markers of PMS and PMDD.

The study used intravenous magnesium, an unconventional method, administered acutely without long-term supplementation. Short bursts of supplementation with this low magnesium level are unlikely to bring about significant changes in women's status or address deficiencies. A more comprehensive approach, combining intravenous injection with dietary supplementation until reaching magnesium sufficiency, could have provided insights into symptom recovery. The study did not bring women to a magnesium sufficiency level that would reveal the potential benefits of magnesium supplementation for PMDD. The authors' motivations are questionable, given the poor experimental design and data analysis choices that could have allowed for a more refined analysis.

In contrast, an Italian study by Facchinetti et. al. (Facchinetti, Borella, Sances, Fioroni, Nappi, & Genazzani, 1991) [11] found:

“To assess an oral Mg2+ preparation's impact on premenstrual symptoms, a randomized study involved 32 women with confirmed PMS. After a 2-month baseline, participants received a placebo or Mg for two cycles, followed by Mg2+ for two cycles. Magnesium pyrrolidone carboxylic acid (360 mg Mg2+) or placebo was administered three times daily from the 15th day of the menstrual cycle. Blood samples for Mg2+ measurement were taken premenstrually, during the baseline, and in the second and fourth treatment months. The "pain" cluster score decreased in both groups during the second month, with Mg2+ influencing the total Menstrual Distress Questionnaire score and the "negative affect" cluster. Women assigned to treatment showed increased Mg2+ in lymphocytes and polymorphonuclear cells during the second month, suggesting Mg2+ supplementation as an effective treatment for premenstrual symptoms linked to mood changes.”

In this study, it's evident that magnesium supplementation doesn't alleviate symptoms in the first month. Unlike previous studies that observed results after more than a month of supplementation, this study was conducted before the study by Khine et al. Those authors, however, designed their study to only assess the effects of supplementation within 2 days after magnesium infusion, which is a flawed approach. Another study in the United Kingdom by Walker et al. showed no effect in the first month of supplementation but found a significant impact on bloating, a challenging PMS symptom, in the second month. This underscores the importance of considering a more extended timeframe for assessing the effects of magnesium supplementation.

“Analysis of variance for 38 women revealed no effect of Mg2+ supplementation compared to placebo in any category in the first month of supplementation. However, in the second month, there was a significant reduction (p = 0.009) in symptoms of PMS-H (weight gain, swelling of extremities, breast tenderness, abdominal bloating) with Mg2+ supplementation compared to placebo.”

It is noteworthy that the study conducted by Walker et al. was cited by Khine et al., but its conclusions were not considered in the design of the latter study. If two separate studies by different research groups consistently show no effect in the first month of supplementation, it raises questions about why a study would be designed to observe effects within only two days of administration.

Subsequent to the studies by Khine et al., further research has explored magnesium's role in the severity of PMS and PMDD. Ebrahimi et al. (2012) found that after two months of magnesium supplementation, all PMS scores were reduced compared to the placebo. Significant differences were observed in craving, water retention, and anxiety symptoms. While symptoms of depression and somatic changes also decreased, statistical significance was not reached at this sample size.

This study also examined the effects of vitamin B6, which exhibited a similar pattern of symptom relief as magnesium supplementation but had a more pronounced impact on depression symptoms than magnesium. Vitamin B6 functions as a cofactor in various enzyme reactions in amino acid, glucose, and lipid metabolism, and it also serves as an antioxidant. [14]

Morris et al. measured blood levels of vitamin B6 as plasma pyridoxal 5'-phosphate (PLP) and observed a marked difference in plasma PLP levels between women of childbearing age (ages 13 to 54) and their male counterparts. The study noted significantly lower PLP levels in women of childbearing age compared to males in a similar age group. Notably, data indicated that oral contraceptive users exhibited extremely low plasma PLP levels, with three-quarters of women using oral contraceptives without vitamin B6 supplements experiencing vitamin B6 deficiency."

Low vitamin B6 levels were observed in menstruating women with past oral contraceptive use, with 40% displaying inadequate plasma pyridoxal 5'-phosphate (PLP) levels. Homocysteine levels were measured, showing no elevation in current oral contraceptive users, but former users had significantly higher homocysteine concentrations than non-users. This suggests that oral contraceptive use may impact vitamin B6 status, with effects potentially masked during use but revealed afterward.

Homocysteine (Hcy) levels, indicative of inflammation, correlate with markers like HsCRP, IL-6, and TNFα in acute coronary syndrome patients, with positive associations to the number of diseased vessels (Oudi et al., 2010) [17]. A recent study by Bertone-Johnson et al. (2014) [18] found that markers of chronic inflammation are linked to menstrual symptom severity and premenstrual syndrome (PMS). Affective menstrual symptoms relate linearly to IL-2 levels, and physical/behavioral symptoms correlate with IL-4 and IL-12 levels. Women meeting PMS criteria have significantly higher levels of IL-4, IL-10, IL-12, and IFN-γ. While this study didn't assess homocysteine, Morris et al. (2007) [19] provide pertinent data.

Treating Inflammation

Treatments for inflammation typically involve NSAIDs, which address internal enzyme-driven inflammation but not external sources like smoking. NSAIDs are akin to preventing campfire feeding without addressing the surrounding blaze. Smoking's positive correlation with PMS severity supports this (Ju et al., 2014) [20].

Antioxidants directly combat free radical effects, alleviating pain, protein and DNA damage. Vitamin B6, vital as an enzyme cofactor and antioxidant, can be crucial during inflammation, potentially consumed as an antioxidant before reaching its enzymatic destinations.

Adequate vitamin B6 intake is challenging, especially due to variable absorption when co-administered with drugs. Many substances, like contraceptives, alcohol, and certain medications, hinder B6 absorption. Interactions with other medicines are also possible (Natura Foundation) [21].

Reviewing B6 dosing reveals a wide therapeutic index. The US RDA is 1.2 to 1.7mg per day according to the National Institutes of Health (NIH) factsheet on vitamin B6.

  
    Age
    Male
    Female
    Pregnancy
    Lactation
  

    Birth to 6 months
    0.1 mg*
    0.1 mg*
    –
    –
  

    7 – 12 months
    0.3 mg*
    0.3 mg*
    –
    –
  

    1 – 3 years
    0.5 mg
    0.5 mg
    –
    –
  

    4 – 8 years
    0.6 mg
    0.6 mg
    –
    –
  

    9 – 13 years
    1.0 mg
    1.0 mg
    –
    –
  

    14 – 18 years
    1.3 mg
    1.2 mg
    1.9 mg
    2.0 mg
  

    19 – 50 years
    1.3 mg
    1.3 mg
    1.9 mg
    2.0 mg
  

    51+ years
    1.7 mg
    1.5 mg
    –
    –
  

* Adequate Intake (AI) (National Institutes of Health, 2011) [22]

This level of adequate intake is suspect due to the unusually low blood level of 20nmol/L B6 used to calibrate the level of intake.

PLP concentrations exceeding 30 nmol/L traditionally indicate sufficient vitamin B6 status in adults (Shils et al., 2012) [23]. However, the Food and Nutrition Board at the Institute of Medicine set a plasma PLP level of 20 nmol/L as the main indicator for Recommended Dietary Allowances (RDAs) (Institute of Medicine, 1998) [24]” (National Institutes of Health) [25].

The Tolerable Upper Intake Level (UL) for B6 supplementation in adults is 100 milligrams, half the amount with no adverse effects on study subjects.

“Studies in patients treated with vitamin B6 (average dose of 200 mg/day) for up to 5 years found no evidence of this effect. Based on limitations in the data on potential harms from long-term use, the FNB halved the dose used in these studies to establish a UL of 100 mg/day for adults.” [26] (National Institutes of Health)

Even with a 100 milligram UL, the highest RDA dose of 1.7 mg the therapeutic index for this vitamin is 58.8. Using the quantity that has shown toxicity of reversible neuropathy at 500mg/day gives a therapeutic index of 294; an exceptionally safe vitamin by any standard.

Transdermal Administration

Interactions between orally consumed medications and orally consumed vitamins is a common problem. One common complaint prior to menstruation is diarrhea, which can impair absorption of B6, which may make the oral administration hit and miss. These problems with oral administration have a very simple answer- topical administration.

In 1985, Russian researchers Gurochkina et. al. (Gurochkina, Koroleva, Avakumov, & Smirnova, 1985) [27] found that pyridoxal phosphate had vitamin B6 activity when applied to the skin of rats. This form of vitamin B6 is therefore likely to have much more reliable absorption and consistent bioavailability compared to other forms of B6 administered orally.

Pyridoxal phosphate has another important advantage over pyridoxine, it has reduced or completely eliminated toxicity when compared to pyridoxine. According to studies conducted by Levine and Saltzman:

“The coenzyme (pyridoxal 5-phosphate) did not cause clinical signs or lesions similar to those produced by pyridoxine even when injected in maximum tolerated doses. Neither a protein-deficient diet nor bilateral nephrectomy changed the results with the vitamers.”(Levine & Saltzman, 2004) [28]

Topical application is therefore an effective and safe means for B6 administration. However, bioavailability of topical applications are typically low, since the only factors driving the movement of these compounds through the skin are the forces of diffusion and translocation by transporters. Enhancing the rate of B6 movement through the skin would allow this route of administration to be much more effective. Penetrating agents can be utilized to enhance delivery, such as glycerin.(Theratech I. , 1993) [29]

Iontophoresis is an additional method of improving permeability of skin to drugs using a flow of ions induced by electrochemical activity. Translocation of pyridoxine phosphate through the epidermis of the skin is predicted to occur for solutions below a pH of 4 (positively charged) and above a pH of 7 (negatively charged). See figure 1 below from dos Santos et. al.(Sci Flo Brazil, 2010) [30]

Figure 3 - Fractional distribution of pyridoxine hydrochloride in its possible forms according to pH values, according to the experimentally determined Ka1 and Ka2 values.

Iontophoresis of pyridoxine hydrochloride and pyroxidine-5 phosphate should be quite efficient for transport of these vitamers through the skin. Typical iontophorisis utilizes a positive and negative pad with a battery or other power source to create ions under these pads via electrolysis of water to H+ and OH- ions. The H+ ions drive the positively charged vitamin into the skin at the anode or positive (+) side of the device and simultaneously drive the negatively charged vitamin into the skin at the cathode or negative (-) side of the device.

The Naked Electron’s Distinct Advantages Over Both Typical Molecular Antioxidants and NSAIDs.

They leave no waste material behind - Unlike a molecular antioxidant, which upon donating its electron becomes waste, a naked electron gets wholly consumed by the free radical.
They are able to act at a distance - Molecular antioxidants need to come into direct contact with a free radical to donate their electron, whereas the naked electron from magnesium metal can utilize its high reducing potential voltage (2.37V), to push the electrons and neutralize free radicals away from the source.

Unlike NSAIDs, they can quench any oxidizing agent regardless of the source - By their nature, NSAIDs can only inhibit enzymes that produce oxidizers. To use an analogy, NSAIDs prevent people at the campground from adding fuel to the campfire, but can do nothing about sources of inflammation that are exogenous. Exogenous sources would be excess sugars, radicals from cigarette smoking, or toxins such as paraquat or pollution. The naked electron doesn’t discriminate when it comes to the source of the radicals, and will neutralize any radicals that occur within the range of the patch.

Can bypass the digestive system and provide highly targeted relief and vitamin delivery – Most dietary vitamins and antioxidants get destroyed as they make their way through the digestive system, while the ones that do make it through are distributed diffusely throughout the body, with no strong way to direct where they go. NSAIDs take a heavy toll on the user’s digestive system and liver, plus they create the potential for lots of side effects if taken in excess. The amount of naked electrons being delivered far exceeds any dose of antioxidants that is possible to be eaten and absorbed through the digestive system. As such, the patch is able to provide effects that are not reproducible by normal antioxidant intake and will neutralize the free radicals and create a potent anti-inflammatory effect within the vicinity of the patch. The patch also has the ability to deliver positive ions like magnesium and potassium directly to desired areas to help initiate various enzymatic effects.
Allow vitamins to fulfill their higher purpose – Many vitamins double as antioxidants and play a crucial role as enzyme cofactors. By being in the presence of large amounts of powerful antioxidants via the naked electrons, the vitamins are protected from oxidation and no longer need to be reduced to the role of a simple antioxidant. Naked electron therapy allows vitamins like B6 to fulfill their specialized role as an enzyme cofactor instead thus making them more useful to the user.

Final Words

Lunapatch, with its concentrated transdermal delivery of naked electrons and minerals, offers targeted pain and symptom relief for localized menstrual cramps. This potent anti-inflammatory technology should be applied specifically for known sources of pain, such as menstrual cramps. It is essential to avoid using human half-cell electron donation technology for unidentified sources of pain or medical conditions. If pain persists beyond three days, consult a healthcare practitioner to explore potential underlying medical issues.

Menstrual pain is particularly suited to naked electron therapy because it has a predictable onset as well as a predictable endpoint. If you experience symptoms that continue beyond the end of menstrual bleeding, please obtain a healthcare practitioner’s advice and seek a more specific treatment for your condition.

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