Vitamin D Supplementation May Help Primary Dysmenorrhea

Primary dysmenorrhea is defined as menstrual pain without any pelvic pathology: Your average case of menstrual cramps, not caused by endometriosis. This is the most common menstrual symptom in adolescent girls and young women. The onset of menstrual pain usually occurs just before or at the first onset of the menstrual flow and typically lasts a half day to three days. Some women have additional symptoms such as headache, fatigue, and even nausea/vomiting, and diarrhea.

In the current double-blind, randomized, placebo-controlled clinical trial in Iran in women, aged 18 to 32 years, with regular menstrual cycles had a pain score of 4 or more out of an 11-point rating scale. These women also had a laboratory value of 25-hydroxyvitamin D < 30 ng/mL, which means some were insufficient (20-30 ng/mL) and some were deficient (< 20 ng/mL). There were 58 participants in the vitamin D supplement group and 58 in the placebo group. Women received vitamin D3 capsules 50,000 once weekly for eight consecutive weeks or placebo.

Results: The serum level of 25 (OH)D significantly increased from 20 to 37 ng/mL in the vitamin D group and no significant changes in the placebo group. Even with this robust dosing of vitamin D for eight weeks, 24% of the women receiving vitamin D supplements still showed low levels of 25(OH)D < 30 ng/mL at week 8. A significant change in pain intensity was found in the vitamin D group and no significant change in the placebo group. The significant reduction in pain intensity was measurable at week 4 (the first menstrual period), as well as week 8. The average pain intensity at baseline was 7.0 +1.7, 6.3 +1.7 at week 4,and 5.6 +1.7 at week 8.

There was also a significant change in the number of days with pain in the vitamin D group and no significant change in the placebo group. By week 8, the reduction in number of days went from two at baseline to one at week 8. Even the number of pain relief medications used per day was reduced in the vitamin D group by half vs no significant change in the placebo group. Lastly, there were even improvements in the systemic symptoms associated with their dysmenorrhea in the vitamin D group, including headache severity and diarrhea with no significant change in the placebo group.

Commentary: One of the things I was curious about was whether or not there was an association between the increase in serum vitamin D level and the improvement in pain intensity. The researchers found no such correlation and surprisingly, there wasn’t even a difference in pain intensity in the vitamin D group with those who did achieve normal serum levels (>30 ng/mL) and those who did not achieve that.

A suggested mechanism causing primary dysmenorrhea is the increased production of prostaglandins in the endometrium (line of the uterus). This rise in prostaglandins in women with primary dysmenorrhea increases uterine tone and high-amplitude contractions. Both upregulation of cyclooxygenase activity and prostaglandin synthesis are generally observed in women with primary dysmenorrhea. Consequently, whether herbal or pharmaceutical… those treatment interventions that are non-steroidal anti-inflammatories and inhibit the expression of cyclooxygenase enzyme that is involved in the synthesis of prostaglandin should be considered first line options for treating acute primary dysmenorrhea. The herb ginger root has some published research for this purpose.

Given the frequency of vitamin D insufficiency or vitamin D deficiency, the possible role of these insufficient levels should be considered as a possible role of causing or exacerbating primary dysmenorrhea.

Rahnemaei F, Gholamrezaei A, Afrakhteh M, et al. Vitamin D supplementation for primary dysmenorrhea: a double-blind, randomized, placebo-controlled trial. Obstetrics Gyn Sci. 2021, May 18 (epub ahead of print).

Unexplained Fatigue, Fibromyalgia in Menopausal Women

Symptoms of fatigue and generalized aches and pains is a common discussion in my women’s health practice. These symptoms also have some specifics related to menopausal women. Fatigue is frequently reported by menopausal woman. There are many possible explanations, including iron deficiency anemia, hypothyroid, insomnia, depression, allergies, non-iron deficiency anemias, chronic disease, chronic pain, adrenal dysregulation, Lyme disease, chronic fatigue syndrome, chronic Epstein Barr Virus (EBV), fibromyalgia syndrome (FMS), multiple chemical sensitivities (MCS), congestive heart failure, chronic lung disease, ischemic heart disease, menopause…and there’s even more.

Fatigue is considered chronic if it has been present for at least six months. This list of possible causes requires a comprehensive history, physical exam, and select laboratory testing. Unfortunately, the usual and customary testing may identify the cause of the fatigue in only about 1 in 20 cases…not a very good statistic. A well trained and experienced naturopathic physician or integrative medicine physician has some expanded tools in testing and thinking, which help them consider some of the more challenging conditions to diagnose such as EBV, adrenal dysregulation, fibromyalgia, and MCS. If a cause of the chronic fatigue is not adequately diagnosed, some just call it chronic fatigue syndrome; but this is actually a distinct clinical diagnosis of its own.

It’s important to consider either CFS or fibromyalgia in women with post-exertional malaise. This is described as a prolonged increase in fatigue disproportionate to the amount of physical, emotional, or mental exertion that occurred. This is a particular characteristic of CFS or fibromyalgia. Frankly, chronic fatigue syndrome is not a very well understood condition but can be debilitating with its fatigue that is only minimally helped by rest. It is common for those with CFS to report non-refreshing/non-restorative sleep, post-exertional malaise that can be experienced with even small exertions like vacuuming, intolerance of body position changes of sitting/lying to standing called orthostatic intolerance, and cognitive impairment. Fibromyalgia is described currently as a central sensitization syndrome that is characterized by amplification of pain signals that our out of proportion to the amount of sensory input. This is called hyperalgesia. Even normal touch can generate pain, called allodynia. Both CFS and FMS have been associated with post-viral syndromes, including coronaviruses.

There is an overlap of the diagnostic criteria for FMS and CFS. Up to 70% of patients with fibromyalgia meet the diagnostic criteria for cardiovascular disease and 35% to 70% of patients with CFS meet the criteria for fibromyalgia. The most common age of incidence of FMS is during the teen years and during the 30s, and the typical age of onset of fibromyalgia is between ages 20 and 50 with increasing prevalence closer to age 50. The predominant view is that at least 80-90% of individuals with FMS are women, although other studies report about 60%. Why it is so much more common in women is not exactly clear, but there are links between a decline in estrogen and menopause and enhanced chronic pain symptoms. There is also evidence that women report worsening of their fibromyalgia symptoms around their final menstrual period. However, new onset aches and pains can be quite common in perimenopause/menopause, and they may or may not meet the diagnostic criteria for fibromyalgia. While there may be this hormonal connection with FMS, there is no clear evidence that taking hormone therapy improves fibromyalgia-associated pain, although some women do experience pain improvement with hormone therapy and their fibromyalgia symptoms—and sometimes also their osteoarthritis symptoms and non-FMS/non-OA aches and pains that I call rheumatism. Menopause is also often associated with not only worsening fibromyalgia pain but worsening fatigue (whether it’s CFS or not), along with sleep disruption. Remember that improving sleep can improve fatigue, including CFS, and improve FMS pain.

We have a long way to go in not only understanding FMS and CFS, but that also means we have a long way to go in effective treatments, whether natural medicine and/or conventional medicine.

Consider Saffron for Fibromyalgia

Fibromyalgia (FM) is considered a neurological disorder with chronic and widespread musculoskeletal pains. It can also be associated with mild to severe fatigue, anxiety, depression, sleep disturbances, hypersensitivities to light/sound/touch, digestive problems, headaches, and cognitive difficulties. More women than men have FM.

While we do not understand what causes fibromyalgia, it appears that it is multifactorial and not the same cause for every patient, but includes genetics, infections with some illnesses triggering or aggravating fibromyalgia, and physical and/or emotional trauma/significant stressors.

It is considered neurological because there appears to be an abnormal increase in certain levels of select neurotransmitters in the brain that signal pain. In addition, the pain receptors in the brain of those with FM develop a pain memory and become more sensitive with a lower threshold to reacting to the pain signals.

Both conventional and natural medicine has yet to determine a clear cause and as yet to offer a reliable and successful treatment approach. Conventional treatment may include pain relievers and antidepressants. Duloxetine, aka Cymbalta, is an approved treatment for FM. It may help to reduce the pain and improve the fatigue and mood. Muscle relaxants and anti-inflammatories may offer some help along with medications such as gabapentin or pregabalin. Indeed, there is a need for expanded options as those in natural medicine are not sufficient either, such as vitamin D, magnesium, curcumin, ribose and others.

Human and animal studies indicate that saffron has antidepressant, antioxidant, and neuroprotective activity. As such, it may be a potential option for FM treatment, or at least part of a FM comprehensive treatment plan. The current randomized, double-blind, controlled trial compared the effects of saffron and duloxetine on symptoms in patients with FM. Fifty-four patients with FM, ages 18-60, were enrolled in a trial in Iran. Patients were included if they had a diagnosis of FM according to the criteria set forth by the American College of Rheumatology and had pain scores >40 out of 100 using a Visual Analog Scale (VAS).

Patients were randomly assigned to take one capsule containing 30 mg duloxetine or one capsule containing 15 mg saffron extract daily during the first week. Patients then took two capsules of duloxetine or saffron daily during the second week and continued at that dose through a total of two months. Primary outcomes were changes in Hamilton Rating Scale for Depression score, Fibromyalgia Impact Questionnaire score, and Brief Pain Inventory pain score from baseline to eight weeks. Secondary outcomes were changes in VAS pain score, fatigue assessments, and Hospital Anxiety and Depression scores from baseline to eight weeks. Patients were instructed to avoid taking medications that could affect FM, during the study.

Mean scores for all outcome assessments improved after eight weeks in both the saffron and duloxetine groups and were not statistically significantly different from each other. There was no significant difference in the number of adverse events in either group.

Commentary: It is easy to get excited by saffron recently…studies in depression, ADHD in children, fibromyalgia and PMS. The current study is certainly good preliminary evidence of a measurable level of improvement in symptoms of fibromyalgia with this dose of saffron. Saffron does have active constituents that have anti-inflammatory and antioxidant effects in the central nervous system and have been shown to increase levels of key neurotransmitters, including serotonin, norepinephrine, and dopamine. The current trial did lack a placebo arm, the study was a small number of individuals, and the study was short in duration. These would all be considered weaknesses of the study, but the study does lay important groundwork for saffron being part of a treatment strategy for those suffering from fibromyalgia.

Shakiba M, Moazen-Zadeh E, Noorbala AA, et al. Saffron (Crocus sativus) versus duloxetine for treatment of patients with fibromyalgia: A randomized double-blind clinical trial. Avicenna J Phytomed. November-December 2018;8(6):513-523.