Treatment of dysmenorrhea only knows ibuprofen? There are actually many options!

Author / Wang Xue

Hospital / Jilin Provincial Maternal and Child Health Hospital

Dysmenorrhea is defined as obstructed menstrual discharge or painful menstruation. The causes of dysmenorrhea are complex and varied, with a prevalence of about 16.8% to 81.0% [1], making it a common disease in women. The severity of dysmenorrhea varies from patient to patient, and 20% of women may have severe dysmenorrhea affecting their lives and work. Dysmenorrhea can occur from the onset of menarche or gradually develop after menarche.

Depending on the etiology, dysmenorrhea can be divided into two categories: primary dysmenorrhea and secondary dysmenorrhea.

The former refers to dysmenorrhea without pelvic organic lesions, which occurs mostly related to prostaglandin synthesis and release abnormalities, abnormal uterine contractions, and neurological and psychiatric factors.

The latter is dysmenorrhea caused by pelvic organic diseases, common causes of endometriosis (referred to as "endometriosis"), adenomyosis, obstructive malformations of the reproductive tract, etc. Endometriosis is a common disease in women of childbearing age, with an incidence of about 5% to 10%, which is one of the important causes of dysmenorrhea in women, and Hansen et al. have reported that 70% to 90% of dysmenorrhea women may have endopathy [2].

General treatment

Emphasis on psychotherapy shows that mild discomfort during menstruation is a physiological response, and that eliminating tension and concern can relieve pain. Adequate rest and sleep, regular and moderate exercise, and smoking cessation all help to relieve pain. When the pain is unbearable, it can be supplemented with medication.

drug therapy

For patients with primary dysmenorrhea, NSAIDs and COCs are commonly used treatments

01

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs are the most commonly used first-line drugs that inhibit prostaglandin synthesis by inhibiting cyclooxygenase (COX), thereby relieving the spastic contractions of the uterus caused by prostaglandins and alleviating dysmenorrhea [3]. Many studies have shown that the content of menstrual prostaglandins is indeed reduced after taking the drug. Treatments can be up to 80% effective. Menstruation is the beginning of menstruation to take the drug effect is good for 2 to 3 days.

NSAIDs, which include traditional non-selective COX inhibitors and selective cyclooxygenase-2 (COX-2) inhibitors, are the most widely used class of drugs in the world because of their anti-inflammatory and analgesic effects. Commonly used non-selective COX inhibitors include: acetaminophen, indomethacin, bischlorophenolic acid, ibuprofen, etc.; selective COX-2 inhibitors include: celecoxib, rofecoxib and nimesulide.

The results of large RCT studies have shown that highly selective COX-2 inhibitors reduce the incidence of severe gastrointestinal adverse events compared with non-selective COX inhibitors, suggesting that selective inhibition of COX-2 improves gastrointestinal safety. This is due to the fact that COX-1 on the stomach wall can promote blood flow to the stomach wall, secrete mucus and bicarbonate to neutralize stomach acid and protect the gastric mucosa from damage. Non-selective inhibition of COX-1 on the gastric wall can cause gastrointestinal damage, and symptoms include gastric and duodenal ulcers, gastric bleeding, gastric perforation and a series of gastrointestinal reactions, which is also a typical adverse reaction of non-selective COX inhibitors.

The U.S. Food and Drug Administration (FDA) specifically approves nonsteroidal anti-inflammatory drugs for the treatment of dysmenorrhea as shown in the table below.

In addition, acetaminophen can also be used to relieve dysmenorrhea, the drug is generally safer, it has a fever-reducing, mild analgesic effect in therapeutic doses (0.25 to 0.5 g per oral dose, 3 to 4 times a day), and the toxicity to the gastrointestinal tract and cardiovascular system is low. Acetaminophen is recommended not to exceed 2 g per day [4].

Table 1 NSAIDs for dysmenorrhea drugs

Therefore, clinicians should not only consider the anti-inflammatory and analgesic effects when selecting NSAIDs, but also weigh the risk of gastrointestinal and cardiovascular adverse events according to the patient's clinical background, and safely and reasonably select NSAIDs.

If there is no significant improvement in dysmenorrhea symptoms for 3 months with NSAIDs, a switch to hormonal therapy should be considered [5].

02

Combined oral contraceptives

Relieves dysmenorrhea and reduces menstrual flow. Suitable for dysmenorrhea women who require contraception, the effect is more than 90%. Combined oral contraceptives are the first-line treatment for endopathic-related pain [6].

Compound oral contraceptives have a dual effect, on the one hand, they can inhibit the growth of the uterine lining, reduce the amount of blood, and reduce the production and release of prostaglandins; on the other hand, they can inhibit ovulation, reduce the content of estrogen in the blood, and reduce the levels of prostaglandin, vasopressin and oxytocin in the blood, thereby inhibiting uterine activity. Not only that, due to the inhibition of hypothalamic-pituitary-ovarian axis function, the level of estrogen in the body is equivalent to the early follicular stage, and the content of endometrial prostaglandin is also the lowest, thus achieving the effect of treating dysmenorrhea.

Combined oral contraceptives have a long history of use in the treatment of endopathy and are recommended as second-line therapy in patients with menorrhagia [7]. However, oral contraceptives should be recommended with caution in patients over 40 years of age, as they may increase the risk of thrombosis or even pulmonary embolism. Especially when there are risk factors, such as smoking, obesity, hypertension, abnormal lipid metabolism, and a history of thrombotic disease.

03

Other drugs

Calcium channel blockers: These drugs interfere with the passage of calcium ions through the cell membrane, and prevent calcium ions from being released from the intracellular inventory, inhibiting the flow of calcium ions into the cell through the uterine smooth muscle cell membrane, thereby inhibiting smooth muscle contraction, relieving uterine spastic contractions, expanding blood vessels, and improving uterine blood supply, so it can treat dysmenorrhea.

In addition, antispasmodic sedatives, vitamin B6, vitamin E, etc. are all effective drugs for the treatment of primary dysmenorrhea, and are also widely used in clinical practice.

For patients with secondary dysmenorrhea due to endeopathy, first-line treatment agents are NSAIDs, COCs, and highly potent progesterones. Second-line treatment includes gonadotropin-releasing hormone agonists (GnRH-a) and levonorgestrel intraguanatic sustained-release systems (LNG-IUS).

Progesterone drugs

Relieves dysmenorrhea and reduces menstrual flow.

1. Dinoprogesterone

In recent years, a new progestin, dienogest, has been marketed in Japan and Europe for the treatment of endeopathy, with good efficacy [8].

Denofestin can directly inhibit the proliferation of endometrial interstitial cells, reduce the synthesis of aromatase, COX-2 and prostaglandins, thereby inhibiting the development of endologic lesions and inhibiting pain. Dinoprogesterone is a highly potent progestin, and the main adverse reactions are irregular vaginal bleeding, breast swelling, nausea, irritability, and depression [9]. Most patients have a good tolerance to denofgesin.

2. Didragestrel

Didraprogesterone is similar in structure to progesterone, has simple progesterone activity, no estrogen, androgen or mineralocorticoid activity, has unique advantages in the treatment of adolescent dysmenorrhea, fertility requirements and pain treatment in perimenopausal patients, has little impact on liver function, and is a new choice for long-term drug treatment of endopathy.

GnRH-a

It can be effective, rapid in relieving pain, treating menorrhagia, and reducing uterine volume [10].

GnRH-a effect is similar to natural gonadotropin-releasing hormone (GnRH), because of its strong affinity with the pituitary gland GnRH receptor, and low sensitivity to peptidase decomposition, so its activity is tens or even hundreds of times higher than the natural GnRH, long-term continuous application, the pituitary GnRH receptor is exhausted, resulting in low estrogen status in the body, temporary menopause.

At present, commonly used GnRH-a drugs are leuprolide, gosereline, tripralin and so on. GnRH-a is effective in relieving pain, especially moderate to severe pain. GnRH-a is effective in treating dysmenorrhea, but is expensive and causes a low estrogen status that can lead to severe perimenopausal symptoms and irreversible bone loss, so GnRH-a should not be used for a long time.

LNG-IUS

May be used as the treatment of choice in patients with menorrhagia in patients with adenomyosis [11].

LNG-IUS can cause locally high progesterone concentrations, inhibit endometrial proliferation, reduce local vascular congestion, thereby reducing menstrual flow and reducing dysmenorrhea. LNG-IUS is indicated in patients who require contraception for a long period of time and have good patient compliance, but may cause irregular bleeding or amenorrhea [12].

Finally, the choice of treatment for dysmenorrhea should be based on the patient's age, fertility requirements, primary disease, pain level, and adherence. The choice of empiric therapy should be based on the patient's individual circumstances, monitor the patient's pain symptoms and changes in the results of auxiliary examinations during treatment, and change the treatment plan at the right time.

Author: Wang Xue

Curator: Dongdong

Illustration: Homemade

Caption: Stand Cool Helo

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