Menstrual cycle

The menstrual cycle plays a role in the variation of symptoms and symptom severity in many immunological, neurological, and female predominant diseases.

Follicular Phase
At the beginning of a woman's cycle, the hypothalamus begins to secrete Gonadotropin Releasing Hormone (GnRH), stimulating the pituitary to create Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), which travel to the ovaries. FSH causes follicles in the ovaries to begin to mature. Several follicles, each of which stores an egg, begin to grow as they mature, and in the process release estrogen. This estrogen produces a negative feedback during the first 10 days of the cycle that tells to the pituitary to inhibit the release of LH. It is important to note that low levels of estrogen will inhibit the release of LH from the pituitary, while high levels will stimulate it.

Ovulation
As estrogen continues to rise due to the maturing follicles, it also causes FSH levels to fall steadily (low estrogen levels trigger the release of FSH). Around day 10 of the cycle, estrogen levels reach a threshold which stops the negative feedback of LH and begins a positive one resulting in the secretion of LH by the pituitary. The resulting spike in LH triggers the most mature follicle to release an egg (or oocyte); this is called ovulation.

Luteal Phase
After ovulation, the empty follicle will begin to die. This dying follicle is called a corpus luteum. As the corpus luteum degrades, it secretes three hormones: estrogen, inhibin, and progesterone. Inhibin provides a negative feedback to the pituitary to suppress the production of FSH. Progesterone provides a similar feedback to prohibit the release of GnRH, which in turn decreases the levels of LH and FSH. It also stimulates endometrial growth (the interior lining of the uterus).

As the corpus luteum degenerates, it will secrete fewer and fewer hormones, and progesterone, estrogen, and inhibin will steadily decrease. In the absence of fertilization, the decreasing levels of progesterone can no longer maintain the lining of the uterine wall, so the wall dies and sheds out of the body, resulting in menstruation. This decrease in progesterone also allows for the secretion of GnRH to begin again, and the cycle repeats.

Immune changes
Populations of Tregs increase peak just before ovulation and bottom out during the luteal phase, just before menstruation.

Progesterone and estrogen have anti-inflammatory effects.

Health effects in ME/CFS
Women with chronic fatigue syndrome report higher rates of polycystic ovarian syndrome (PCOS) and anovulatory cycles, higher rates of dysmenorrhea and higher rates of endometriosis.

Women who develop CFS report at higher rates a history of irregular cycles, amenorrhea, anovolutory cycles and sporadic bleeding between periods.

Numerous outbreaks of epidemic myalgic encephalomyelitis noted menstrual irregularities and a tendency toward relapse before or during menstruation.

Health effects in other conditions
The menstrual cycle can have effects on the timing and severity of symptoms of women suffering from many different conditions, including epilepsy, migraines, asthma, rheumatoid arthritis and irritable bowel syndrome.

Many women with epilepsy have patterns of seizure activity linked to their menstrual cycles, called catamenial epilepsy. Seizure activity increases just before ovulation and just before menstruation.

Abrupt estrogen withdrawal, such as what occurs just prior to menstruation, can trigger migraines. Women with rheumatoid arthritis experienced reduced symptoms after ovulation, owing potentially to the anti-inflammatory effects of progesterone and estrogen.

In a retrospective study, 72% of women with fibromyalgia reported a worsening of symptoms just before their periods.

Women with these diseases may experiencing a worsening of symptoms at specific points in their menstrual cycle, particularly just before or around their periods.

Managing premenstrual symptoms
Nonsteroidal anti-inflammatory agents are occasionally effective in women with menstrual migraine, as are beta blockers, calcium channel blockers, ergotamine, antidepressants, estrogen and estradiol.

Pathophysiology of menstrual symptoms
Estrogen may directly affect blood vessels by stimulating nitric oxide release. Women with a history of menstrual migraine had a heightened activation of the nitro oxide and L-arginine pathways, especially during the luteal phase.

Notable studies

 * 2011, Gynecological History in Chronic Fatigue Syndrome: A Population-Based Case-Control Study