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Premenstrual Syndrome

The Menstrual Cycle, Hormones, and PMS

A normal menstrual cycle is characterized by the regular rise and fall of sex hormones, most importantly estrogen and progesterone, culminating in menstruation. The cycle is usually divided into four phases:

  • Follicular phase. During this phase, a rise in follicle stimulating hormone (FSH) causes several follicles (each containing an egg) to begin growing on the surface of the ovary. Under the influence of the pituitary luteinizing hormone, these follicles secrete estradiol, a form of estrogen. This estrogen discourages production of FSH by a negative feedback mechanism, causing a slowdown in growth of the follicles. The estrogen also encourages endometrial (uterine lining) tissue to build up in preparation for a fertilized egg. Eventually, one follicle emerges as the dominant follicle.
  • Ovulation. In this phase, the dominant follicle bursts, releasing an egg into the fallopian tube. This phase is caused by a boost in the production of luteinizing hormone. Ovulation usually occurs around day 14 of the cycle, but the timing varies from woman to woman. Once the egg is in the fallopian tube, it is available for fertilization.
  • Luteal phase. After the egg has been released, the remaining follicle tissue is known as the corpus luteum. During the next two weeks of the menstrual cycle, the corpus luteum secretes an increasing amount of progesterone to prepare the body for early pregnancy and reception of a fertilized egg. If the egg is not fertilized, progesterone levels decline.
  • Menstruation. Menstruation is characterized by low levels of progesterone and estrogen. It occurs when the egg has not been fertilized. In this phase, the built-up portion of the uterine wall sloughs off and passes through the vagina as blood, mucus, and tissue remnants. This sloughing off is caused by contraction of the arterioles that supply the thickened endometrium with blood, as well as the contraction of endometrium smooth muscular wall. These muscular contractions cause cramping and are under the control of cyclooxygenase (COX) enzymes. COX enzymes are nonselectively inhibited by over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs).

Among women with PMS, some form of hormonal dysfunction occurs during the luteal phase. However, PMS is still not well understood, and many theories have been proposed to explain the underlying symptoms. Until the clinical diagnosis of PMS was established, there was significant disagreement as to whether it was a legitimate medical condition.

A number of novel theories have been put forward to help explain PMS. There is evidence that in severe cases, symptoms associated with severe menstrual disorders are caused by a derangement of serotonin, an important neurotransmitter that regulates mood and behavior (Clayton 2006).

Evidence also suggests decreased sensitivity of brain gamma-aminobutyric acid (GABA)-alpha receptors, increased sensitivity of brain motor cells, and disturbances of the hypothalamic-pituitary-adrenal axis, which controls stress hormone levels (Smith 2003; Sundstrom 1998; Rabin 1990). GABA-alpha is an inhibitory neurotransmitter associated with relaxation and a decrease in anxiety.

Together, these effects might account for some of the mood and motor problems commonly seen in PMS. There is also evidence that PMS runs in families, and women with PMS also tend to have a personal or family history of alcohol abuse and mood-related psychiatric disorders (Berga 2005). Also, women with a history of sexual abuse were found to be more likely to suffer from severe PMS. Studies have shown that up to 95% of women who experienced sexual abuse, often at early ages, were likely to suffer from PMS (Golding 2000).

Finally, prostaglandins (hormone-like chemicals that control various bodily functions) may play a role in PMS. Prostaglandins are known to promote smooth muscle contraction and blood vessel dilation, both of which are essential to the normal menstrual cycle. Studies have shown that prostaglandin excretion is disordered in women with PMS compared with women without PMS (Piccoli 1993). Prostaglandin production appears to be significantly lower in the late luteal phase of women with PMS compared with controls, based on a study of 20 women with PMS and 12 controls, while prostaglandin production is much higher in the follicular phase and early luteal phase (Koshikawa 1992).

Hormone Modulation and Menstrual Syndromes

The influence of hormones on PMS and menstrual syndromes has been studied extensively, often with conflicting results. Women typically suffer from PMS during the luteal phase of their menstrual cycle, which is characterized by increasing levels of progesterone and fluctuating levels of other steroid hormones. Hoping to unravel the connection between hormones and premenstrual symptoms, researchers have studied women with PMS to see whether they have abnormal levels of various hormones compared to women without PMS. In one study, researchers found that 20 women with PMS had higher levels of dehydroepiandrosterone (DHEA) and free testosterone during the luteal phase of menstruation, along with reduced levels of allopregnanolone, than did 20 controls (Lombardi 2004). Allopregnanolone is a metabolite of progesterone and an active neurosteroid shown to affect mood and behavior.

Using conventional estrogen-progestin (synthetic progesterone) contraceptives, many studies have examined the role of hormone therapy to control symptoms associated with PMS. These hormone preparations are used to induce a state of anovulation (no ovulation), which allows women to bypass hormonal fluctuations that occur during ovulation and thus, the accompanying symptoms (Mayo Clinic 2005). Unfortunately, evidence of their effectiveness is mixed.

Some women attempt to control their symptoms with progestins, or synthetic progesterone. These drugs have consistently failed to show good results. However, a progestin called drospirenone has been introduced for the treatment of PMS. Drospirenone is derived from a source (17-alpha spironolactone) different from the progestins usually used in oral contraception. It has antimineralocorticoid activity and thus, is not associated with weight gain and fluid retention, unlike some other hormone preparations.

When it comes to hormone modulation to control symptoms of PMS, Life Extension advocates a more natural approach than can be achieved with synthetic estrogens and progestins. Natural, safe progesterones derived from yams can be used in place of progestins. In addition, phytoestrogens, or estrogen-like compounds derived from plants, have shown some efficacy in relieving PMS symptoms. In one double-blind, placebo-controlled, randomized study, phytoestrogens derived from soy were examined for their ability to reduce symptoms of PMS. After 2 months, volunteers experienced reduced headache, breast tenderness, cramps, and swelling during periods when taking soy products compared to placebo (Bryant 2005).

The hormone melatonin, which is usually associated with sleep and insomnia, may also play a role in alleviating symptoms of PMS and PMDD. Melatonin, involved in a variety of mood and anxiety disorders, is intimately related to sex hormones and other hypothalamic-pituitary-adrenal-axis hormones. Studies have shown that melatonin levels are low among women with PMDD (Parry 1989).