Introduction

Tension-type headache (TTH) is the most common headache subtype in the world. It is defined as a headache that is bilateral, pressing or tightening in quality, mild to moderate in severity, with possible light or sound sensitivity, but not both (Table 1) [1]. It is not aggravated by physical activity, nor associated with vomiting. TTH is experienced at some time in the lives of 30% to 80% of the population; the lifetime prevalence of TTH is 69% in men and 88% in women, with a male-to-female ratio of 4:5 [2, 3].

Table 1 International Headache Society criteria
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The pathophysiology of most headache disorders still is unclear, and for TTH, is poorly understood. While it may share features with migraine, such as some similar triggers for headache and an occasional response to triptans, TTH has some unique properties of its own. The male-to-female ratio is much closer than in migraine headaches [4••]. Myofascial trigger points play some role in episodic TTH, implying a peripheral mechanism being involved in the pathophysiology of TTH, whereas in migraine, central mechanisms are primarily involved. There may be a link between TTH and migraine in the form of female sex hormones. For some women, menses is a trigger for TTH, and both pregnancy and menopause may affect their TTH. If hormonal fluctuations actually can trigger TTH, this may imply central mechanisms involved in the pathophysiology of the disease.

The purpose of this article is to discuss how episodic TTH affects women, particularly how TTH can be influenced by changes in sex hormones, and to discuss if the relationship between TTH and sex hormones gives us insight on the pathophysiology of episodic TTH.

Prevalence

TTH is considered a “normal” headache by most people, frequently relieved by over-the-counter medication. The headache can vary in both frequency and duration, from short episodes of mild pain, to frequent, long-lasting, or continuous severe pain. Often, patients do not report TTH to physicians. Though 59% of patients with TTH feel that the headaches interfere with their activity, only 16% of patients consult their physicians for the headache [5, 6]. Studies have shown that 5% of the employed population from ages 25 to 64 years is absent 4 days per year due to headache, and 2% are absent for 20 days per year due to headache [3].

The prevalence rates of TTH vary, with studies showing lifetime prevalence rates of anywhere from 34.8% to 75% of the population [3, 7]. This range could represent the infrequent reporting of symptoms by patients to their physicians. It also may represent the rare episodes many patients have, causing a lack of recall about their infrequent headaches.

The annual incidence for TTH is 14.2 per 1,000 person-years for frequent TTH, with a male-to-female ratio of 5:4 [8••]. Unlike migraine, TTH is only slightly more prevalent in women compared to men. Disability related to TTH is greater than that of migraine, likely related to the higher prevalence of the disease [8••]. Prognosis of TTH has not been analyzed to a great extent. One 12-year longitudinal study from Denmark found that in patients with frequent episodic TTH and chronic TTH, 45% experienced remission, 39% had unchanged frequent episodic TTH, and 16% had unchanged or newly developed chronic TTH at follow-up. Outcome was worse in those with baseline chronic TTH, coexisting migraine, and sleep difficulties and in unmarried individuals [9].

Pathophysiology

TTH originally was thought to be related to stress and tension. The pathophysiology was considered to be related to muscle contraction and ischemia of the head and neck muscles that could be activated by stress/tension [8••]. This theory later was refuted when electromyogram studies failed to show consistent changes in muscle tone in patients with TTH, and muscle lactate levels were found to be normal in patients with TTH performing static exercises [10, 11]. Myofascial factors likely play a role in the pathophysiology of TTH. In patients with TTH, pericranial myofascial tissues are tender compared to healthy patients, and the increased tenderness is correlated with the intensity and frequency of headache [8••]. This implies a peripheral mechanism in the pathophysiology of TTH, with peripheral sensitization of myofascial nociceptors. Recurrent episodes of TTH may lead to central sensitization and excitation of second-order neurons at the level of the spinal dorsal horn and trigeminal nucleus, or impaired descending inhibition of supraspinal neurons, also leading to increase sensitization [12]. This may be triggered by prolonged activation of primary sensory afferents in tender myofascial tissue [12]. Increased central sensitization may decrease antinociceptive activity from supraspinal structures, lowering the threshold for further TTH episodes [8••]. Over time, this can lead to chronic TTH [2].

There seems to be a link between TTH and migraine, though where this link exists is unclear. Many patients with migraine, when asked about their headache history, will describe their first headaches as moderate in severity with no associated features (tension-type in nature). In time, with age or change in life situations, most describe an evolution of their headaches to being more severe in pain, with an onset of associated symptoms. Still, out of the number of patients who ever have had a TTH, only a small portion develops migraine headaches. For these patients, it still is unclear why their TTHs transformed to migraines; is it because their TTHs were a milder form of migraine, or is having TTH a risk factor for developing migraines? It could be that with an increase in frequency of TTH, central mechanisms begin to play a role in the pathophysiology of headache, leading to more migrainous-type symptoms.

Sex Hormones and Tension-Type Headache

The role of sex hormones in TTH may be the link between TTH and migraine. In women, sex hormones are influenced by the menstrual cycle. The menstrual cycle is a normal series of physiologic changes that occur in fertile women. There are four phases of the menstrual cycle: menses, follicular phase, ovulation, and luteal phase, in that order [13]. The average length of the cycle is 28 days. The menstrual cycle is under the control of various sex hormones, such as follicular-stimulating hormone (FSH) and luteinizing hormone (LH), produced in the pituitary gland, and estrogen and progesterone, produced by the ovaries. The interplay of these hormones is what moves the menstrual cycle from one phase to the next (Fig. 1). During menses, all hormone production is low. FSH is stimulated at the end of menses. The rise of FSH stimulates ovarian follicles during the follicular phase. As they mature, follicles stimulate estradiol, a form of estrogen. Estradiol suppresses the production of LH at the end of the follicular phase. When the follicle is near maturity, estradiol levels reach a certain threshold and begin to stimulate LH production. LH production surges before ovulation, triggering a rise in progesterone. Once progesterone levels increase, this causes a small rise in estrogen. The combined increase in estrogen and progesterone reduces the production of FSH and LH during the luteal phase. If the egg is not fertilized, progesterone levels and then estrogen levels fall, signaling the start of the next menstrual cycle [13].

Fig. 1
figure 1

Graphic representation of the fluctuations of different hormones during the phases of the menstrual cycle. Of note, LH, FSH, progesterone, and estrogen levels all are very low during menopause. FSH—follicle-stimulating hormone; LH—luteinizing hormone

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The fall in estrogen levels before menstruation is thought to trigger migraine in 60% of women who have migraines [14]. Headaches in relation to menses are experienced by 14% of women with migraine. Menses is a trigger for headache for 38% to 45% of women with TTH, implying some link between TTH and sex hormones [7, 14, 15].

If an egg is fertilized after ovulation, the embryo produces human chorionic gonadotropin. Similar to LH, this keeps progesterone levels elevated, therefore keeping estrogen levels stable. Postpartum estrogen and progesterone levels begin to drop and reach prepregnancy levels by 5 days after birth [13]. During pregnancy, when estrogen levels are elevated, headaches have a tendency to diminish [15]. This is seen in both migraine and nonmigraine headache, though some studies suggest this finding is more prominent with migraine headaches compared to TTH [15, 16•].

As women age, the ovarian production of estrogen and progesterone reduces, causing infrequent menstrual cycles. When menstruation ceases for 1 year, women are considered to be in menopause and estrogen and progesterone levels are very low. The transition time between normal menstrual cycles and menopause is called perimenopause. During this time, estrogen and progesterone levels fluctuate significantly, sometimes worsening headache. Like migraine, TTH more commonly develops in the second decade of life and can peak again between the ages of 50 and 59 years [7, 17]. This correlates to menarche and menopause in women, two time periods where sex hormones fluctuate [18].

Migraine and TTH are known to share a number of triggers: stress, altered dietary schedule, fatigue, and lack of sleep being the most common (Table 2) [15]. Migraine is known to have some unique triggers of its own, such as weather changes and certain foods [7]. Menses traditionally has been considered a trigger for migraine, with menstrual migraine and menstrually related migraine appearing in the International Headache Society classification system [1]. Though literature review shows the presence of nonmigraine or TTH being triggered by menses, there only has been one study that has formally evaluated the existence of pure menstrual TTH [19•]. In the population studied, 12.7% of women had menstrual TTH or menstrually related TTH (findings were statistically significant). About 3% of this group also had migraines, or were using oral contraceptives. Larger population studies need to be done to further evaluate patients who only have TTH to see what portion of these patients have headache triggered by menses.

Table 2 Features of tension-type headache versus migraine
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The theories on the pathophysiology of TTH do not lend themselves to having hormonal fluctuations as a trigger. During menses, fluctuations in estrogen cause prostaglandin levels to rise, which can decrease pain threshold by affecting descending norepinephrine pain control systems in the brain [17]. In addition to this, falls in estrogen levels produce dopamine receptor hypersensitivity, which lead to elevated prolactin levels that in turn cause opioid dysregulation to occur. Hormone fluctuation causing alteration in central pain pathways triggering migraine is understandable, because the pathophysiology of migraine is thought to be a central process. However, if TTH is primarily a peripheral phenomenon, why would fluctuations in estrogen cause headache? Does hormonal flux triggering TTH give evidence for TTH and migraine sharing common pathophysiological features? It is possible that the pathophysiology of episodic TTH may involve a connection between the central and peripheral nervous system, with triggers activating the trigeminal nucleus, which then somehow causes peripheral sensitization of myofascial nociceptors. It may be that the central process in TTH only is activated once a certain threshold is reached; TTH may begin to look more like migraine beyond this threshold, responding to changes in sex hormones for a small population. This may be where the link between episodic TTH and migraine exists.

Currently, the diagnostic criteria for hormone-related headaches only exist for migraines (Table 1). Even these are listed separately, in the appendix section of the second edition of the International Classification of Headache Disorders (ICHD-II) [1]. Menstrual migraine is defined as a migraine without aura that occurs on day +1/–2 of menstruation in at least two out of three menstrual cycles. Menstrually related migraine is defined as a migraine without aura that occurs on day +1/–2 of menstruation in at least two out of three menstrual cycles, in addition to other times in the cycle. Some consider that hormonal changes are a trigger for headache, but menstrual migraine or menstrual TTH do not warrant their own classifications as separate disorders. This may be true for a large portion of women who have headache both related and not related to menses, but there is a smaller subgroup of women who experience headache only related to menses. More studies need to be done in this subgroup to identify how common migraine features are compared to TTH features during menstrual-related headaches, and if patients actually fluctuate between migraine and TTH during different cycles. This may help show the clinical link between migraine and TTH. During the current revision of the ICHD- II, a revision to the appendix to include “hormonal-related headaches” that can include both menstrual migraine and menstrual nonmigraine, as well as headache related to perimenopause, should be considered.

Conclusions

TTH is the most common form of headache, experienced by most people at some point in life. TTH, especially in its chronic form, is more disabling than migraine, and can have a poor long-term prognosis. In women, TTH can be triggered by menses, may improve during pregnancy, and possibly can improve after menopause. It is unclear if fluctuations in sex hormones imply a central process in the pathophysiology of episodic TTH, or if TTH being triggered by changes in estrogen imply that TTH is on the same spectrum as migraine. Studies focusing specifically on the role of menses, pregnancy, and menopause and episodic TTH would be helpful in clarifying how large a role sex hormone fluctuations play in the frequency of TTH.