Method for assessing severity of premenstrual syndrome by using hippuric acid as index

Abstract

The present invention provides: a method for assessing the severity of premenstrual syndrome by using hippuric acid as an index; and a device therefor.　The present invention also provides: a method for assessing the severity of premenstrual syndrome of a subject by using hippuric acid in a sample derived from the subject as an index; a device for assessing the severity of premenstrual syndrome; and an assessment system for the severity of premenstrual syndrome.

Description

A method for assessing the severity of premenstrual syndrome using hippuric acid as an indicator

[0001] The present invention relates to a method for evaluating the severity of premenstrual syndrome using hippuric acid as an indicator and an apparatus therefor.

[0002] Many women experience physical changes during their menstrual cycle. Physical and / or mental discomfort before menstruation is called premenstrual syndrome (PMS). PMS is a group of symptoms characterized by recurring emotional, behavioral, and physical symptoms before menstruation. These symptoms include various physical symptoms, such as menstrual cramps, and psychological changes, such as mood swings, depression, anxiety, and aggression. Other symptoms of PMS include edema, constipation, drowsiness, lower back pain, lower abdominal pain, headache, fatigue, stiff shoulders, swelling, breast tenderness, dizziness, rough skin, acne, fatigue, lethargy, poor concentration, and irritability. While the cause of PMS is unclear, fluctuations in the female hormones estrogen and progesterone are thought to contribute. These symptoms gradually worsen after ovulation, peak one week before menstruation, and subside within a few days of menstruation.

[0003] Premenstrual syndrome is diagnosed according to guidelines and diagnostic criteria, but these are rarely used due to their complexity and lack of clinical accuracy (J Obstet Gynaecol Res. 2023 May;49(5):1375-1382.: Non-Patent Document 1; Women Health. 2014;54(3):232-44: Non-Patent Document 2). Furthermore, there are no appropriate markers for diagnosing PMS. Therefore, even if a subject is suffering from symptoms suspected to be PMS, they may actually be experiencing symptoms due to other causes, and as a result, incorrect advice or treatment may result in no improvement or even worsening of the symptoms. Therefore, there is a need for a marker that can objectively diagnose PMS.

[0004] J Obstet Gynaecol Res. 2023 May;49(5):1375-1382Women Health. 2014;54(3):232-44Simone et al., Ageing Res Rev 2021 Sep:70:101410Sun et al., Antioxidants 2020, 9(9), 783Huang et al., Redox Biology Volume 16, June 2018, Pages 303-313Zheng et al., J Proteome Res 2013 Dec 6;12(12):5904-1Williams et al., J Gastroenterol. 2009 Jun;104(6):1435-44

[0005] An object of the present invention is to provide a method for evaluating the severity of premenstrual syndrome using hippuric acid as an indicator, and an apparatus therefor.

[0006] The present inventors conducted a comparative analysis of the metabolome of metabolites from biological samples during the luteal and follicular phases of PMS and found that hippuric acid, particularly urinary hippuric acid, can be used as an indicator of the severity of PMS, leading to the completion of the present invention. [1] A method for assessing the severity of premenstrual syndrome in a subject using hippuric acid in a sample from the subject as an indicator. [2] The method of [1], which includes a step of quantifying hippuric acid. [3] (1) In the subject in the luteal phase of the menstrual cycle, if the hippuric acid level is significantly lower than the level in a group with mild premenstrual syndrome, this is an indicator of severe premenstrual syndrome severity; (2) In the subject in the period from the follicular phase to the luteal phase of the menstrual cycle, if the hippuric acid level of the subject increases during this period, this is an indicator of mild premenstrual syndrome severity. [4] Any of the methods of [1] to [3], wherein the sample is urine. [5] The method of any one of [1] to [4], wherein the severity of premenstrual syndrome is caused by increased oxidative stress in the body. [6] A kit comprising a means for measuring hippuric acid in a sample derived from a subject, for assessing the severity of premenstrual syndrome in the subject. [7] The kit of [6], which quantifies hippuric acid. [8] (1) In the subject in the luteal phase of the menstrual cycle, if the hippuric acid level is significantly lower than the level in a group with mild premenstrual syndrome, this is an indicator of severe premenstrual syndrome. (2) In the subject in the period from the follicular phase to the luteal phase of the menstrual cycle, if the hippuric acid level of the subject increases during this period, this is an indicator of mild premenstrual syndrome. [9] The kit of any one of [6] to [8], wherein the sample is urine.

[10] An apparatus for evaluating the severity of premenstrual syndrome, comprising: an input unit for inputting data on the amount of hippuric acid in a sample derived from a subject; a memory unit for storing a correlation between the amount of hippuric acid and the severity of premenstrual syndrome; and an output unit for outputting the severity of premenstrual syndrome from the correlation.

[11] The apparatus according to

[10] , further comprising a processing unit for determining the severity of premenstrual syndrome from the amount of hippuric acid in a sample derived from a subject and the correlation between the amount of hippuric acid and the severity of premenstrual syndrome stored in the memory unit.

[12] The apparatus of

[10] or

[11] , comprising a step of quantifying hippuric acid.

[13] (1) In the subject in the luteal phase of the menstrual cycle, if the hippuric acid level is significantly lower than the level in a group with mild premenstrual syndrome, it is an indicator of severe premenstrual syndrome. (2) In the subject in the period from the follicular phase to the luteal phase of the menstrual cycle, if the hippuric acid level of the subject increases during that period, it is an indicator of mild premenstrual syndrome.

[14] In any of the devices

[10] to

[13] , wherein the sample is urine.

[15] In any of the devices

[10] to

[14] , wherein the aggravation of premenstrual syndrome is caused by increased oxidative stress in the body.

[16] The device for evaluating the severity of premenstrual syndrome provides a lifestyle improvement plan according to the severity of premenstrual syndrome based on the determined severity of premenstrual syndrome of the subject, wherein: the memory unit further stores a correspondence relationship between the severity of premenstrual syndrome of the subject and lifestyle improvements according to the severity of premenstrual syndrome; the processing unit determines the lifestyle improvement plan according to the severity of premenstrual syndrome from the correspondence relationship between the severity of premenstrual syndrome of the subject and the lifestyle improvement plan according to the severity of premenstrual syndrome, stored in the memory unit; and the output unit outputs the determined lifestyle improvement plan.

[17] The device of

[16] , wherein the lifestyle improvement plan is at least one selected from the group consisting of taking ingredients that alleviate the severity of premenstrual syndrome, taking birth control pills, encouraging exercise, quitting smoking, drinking in moderation, and antioxidant supplements.

[18] A system including the device of any one of

[10] to

[17] , wherein the device is connected to a network, and wherein data on the hippuric acid level in a sample derived from a subject is input to the input unit via the network; and the determined severity of premenstrual syndrome is output from the output unit via the network.

[19] The system of

[18] , further including a network-connected terminal device, the terminal device including: a network connection unit connected to the device; and a terminal output unit that outputs, via the network connection unit, at least one selected from the group consisting of the severity of premenstrual syndrome of the subject output from the output unit of the device, and lifestyle improvement suggestions according to the severity of premenstrual syndrome.

[0007] The severity of premenstrual syndrome can be evaluated by using hippuric acid as an indicator.

[0008] 1 shows the menstrual cycle of a subject in an embodiment and the time frame for urine collection and PMS questionnaire administration. During the luteal phase, higher hippuric acid levels indicate milder premenstrual syndrome severity. From the follicular phase to the luteal phase, increasing hippuric acid levels indicate milder premenstrual syndrome severity. Hippuric acid levels are shown for subjects diagnosed with PMS (mMDQ score ≥ 103) and subjects not diagnosed with PMS (mMDQ < 103) during the luteal phase. The change in hippuric acid levels from the follicular phase to the luteal phase for subjects diagnosed with PMS (mMDQ score ≥ 103) and subjects not diagnosed with PMS (mMDQ < 103) is shown. A configuration diagram of a premenstrual syndrome severity evaluation device 10 according to the present invention is shown. The process for determining the severity of premenstrual syndrome is cooperatively executed by hardware resources including an input unit 11, a memory unit 12, a processing unit 13, an output unit 14, and a learning unit 15, all connected via a bus. 1 shows a configuration diagram of a premenstrual syndrome symptom evaluation system 20 including a premenstrual syndrome symptom evaluation device 10 according to the present invention, which is arranged on the Internet.

[0009] The present invention relates to a method for assessing the severity of premenstrual syndrome based on the amount of hippuric acid in a biological sample, particularly urinary hippuric acid, and to an apparatus and system for assessing the severity of premenstrual syndrome.

[0010] [Method for assessing the severity of premenstrual syndrome in a subject using hippuric acid in a sample derived from the subject as an indicator.] The present invention relates to a method for assessing the severity of premenstrual syndrome in a subject using hippuric acid in a sample derived from the subject as an indicator.

[0011] Hippuric acid, along with methylhippuric acid and mandelic acid, is a metabolic product of organic solvents such as toluene, xylene, and styrene absorbed into the body, and its concentration in urine is quantified for the purpose of health management of workers who handle such organic solvents. In healthy individuals, hippuric acid levels in urine increase with age, but it is known that hippuric acid levels in urine decrease and show low values ​​in cases of intestinal bacterial flora imbalance, rheumatic diseases, sarcopenia, etc. (Simone et al., Ageing Res Rev 2021 Sep:70:101410: Non-Patent Document 3). Hippuric acid also promotes renal fibrosis in chronic kidney disease (CKD) by disrupting the antioxidant system driven by the transcription factor NRF2, which regulates the expression of antioxidant enzymes (Sun et al., Antioxidants 2020, 9(9), 783: Non-Patent Document 4). It has also been suggested that hippuric acid increases the production of mitochondrial reactive oxygen species (ROS) in endothelial cells, contributing to endothelial dysfunction (Huang et al., Redox Biology Volume 16, June 2018, Pages 303-313: Non-Patent Document 5). Additionally, hippuric acid has been shown to have low levels in urine from patients with major depressive disorder (MDD) (Zheng et al., J Proteome Res 2013 Dec 6;12(12):5904-11: Non-Patent Document 6), and also in inflammatory bowel disease (IBD) and Crohn's disease (Williams et al., J Gastroenterol. 2009 Jun;104(6):1435-44: Non-Patent Document 7), suggesting its potential as a marker for these diseases. However, there is no literature demonstrating a relationship between hippuric acid and premenstrual syndrome.

[0012] Although the method for measuring hippuric acid is not particularly limited, it is typically measured by high performance liquid chromatography (HPLC). For example, analysis of hippuric acid in urine is carried out by first acidifying the urine, extracting hippuric acid in the urine with a solvent such as ethyl acetate, removing the solvent from the extract by evaporation, dissolving the extract in a mobile phase, and analyzing it by HPLC.

[0013] The biological sample is not particularly limited, and examples thereof include urine, blood, saliva, bone marrow fluid, and interstitial fluid, with urine being preferred.

[0014] The menstrual cycle generally refers to the number of days from the first day of menstruation, counting it as day 1, to the day before the next menstruation begins. While menstrual cycles vary greatly from person to person, they generally occur on a roughly 28-day cycle up until menopause, lasting approximately 3-7 days. The roughly five days from the day menstruation begins are often referred to as menstruation (period), the period from 5 to 12 days later as the "follicular phase," the period from 12 to 17 days later as the "ovulation phase," and the period from 17 to 28 days later as the "luteal phase."

[0015] The present inventors measured hippuric acid levels in biological samples, particularly in urine, during the menstrual cycle and investigated the relationship with the severity of premenstrual syndrome. As a result, they found that the higher the hippuric acid level during the luteal phase, the milder the severity of the premenstrual syndrome in the subject.

[0016] In the present invention, the hippuric acid level "significantly lower than that of a group with mild premenstrual syndrome" may mean that the subject's hippuric acid level is, for example, 90% or less, 80% or less, 70% or less, 60% or less, 50% or more, 40% or less, 30% or less, 20% or less, or 10% or less of the level of a group with mild premenstrual syndrome. The average level of the group with mild premenstrual syndrome is approximately 402 mg / L.

[0017] Furthermore, it has been found that even in subjects whose hippuric acid level increases from the follicular phase to the luteal phase, the severity of premenstrual syndrome is mild.In the present invention, the "increase" of hippuric acid level during the period from the follicular phase to the luteal phase can mean, for example, that the hippuric acid level on the last day of the luteal phase increases by 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 100% or more, based on the hippuric acid level on the first day of the follicular phase.The average change in the value of the group whose severity of premenstrual syndrome is mild is about 0.359.

[0018] The severity of PMS was assessed by a detailed questionnaire (modified menstrual distress questionnaire (mMDQ)) and women with an mMDQ score of 103 or higher were considered to have PMS, based on previous reports and the recommended standard for medical consultation. Without being bound by theory, given that hippuric acid is known to be involved in oxidative stress, low levels of hippuric acid in biological samples such as urine may inhibit the excretion of hippuric acid, which may increase the concentration of hippuric acid in the body and worsen the severity of PMS during the menstrual cycle.

[0019] The method for assessing the severity of premenstrual syndrome according to the present invention can determine the severity of premenstrual syndrome unequivocally by using a predetermined correspondence relationship, and therefore does not require the judgment of a doctor, and can be called a so-called non-diagnostic method. The method of the present invention can be used by persons other than medical professionals, for example, employees of cosmetic stores and employees of beauty salons and other beauty service providers.

[0020] [Kit] Another aspect of the present invention can provide a kit for assessing the severity of premenstrual syndrome in a subject, the kit comprising a means for measuring hippuric acid in a sample derived from the subject.

[0021] The kit of the present invention may include a means for quantifying hippuric acid, which can be determined by referring to the above-mentioned method for measuring hippuric acid.

[0022] The kit of the present invention also provides the following: (1) In the subject whose menstrual cycle is in the luteal phase, if the hippuric acid value is significantly lower than the value in a group whose premenstrual syndrome severity is mild, it is an indicator of the severity of the premenstrual syndrome; (2) In the subject whose menstrual cycle is in the period from the follicular phase to the luteal phase, if the hippuric acid value of the subject increases during that period, it is an indicator of the severity of the premenstrual syndrome.

[0023] [Premenstrual Syndrome Severity Assessment Device] Another aspect of the present invention may relate to a device for assessing the severity of premenstrual syndrome (hereinafter referred to as a premenstrual syndrome severity assessment device). Such a premenstrual syndrome severity assessment device can determine the severity of premenstrual syndrome based on the amount of hippuric acid in a biological sample, particularly urine. This skin condition assessment device specifically includes the following: an input unit 11 into which data on the amount of hippuric acid in a sample derived from a subject is input; a memory unit 12 that stores the correlation between the amount of hippuric acid and the severity of premenstrual syndrome; a processing unit 13 that determines the severity of premenstrual syndrome based on the amount of hippuric acid in the sample derived from the subject and the correlation between the amount of hippuric acid stored in the memory unit 12 and the severity of premenstrual syndrome; and an output unit 14 that outputs the determined severity of premenstrual syndrome. For example, the correlation between the amount of hippuric acid and premenstrual syndrome stored in the memory unit 12 may be a correspondence table, graph, or correlation equation, or may be a relationship between one or more thresholds and the skin condition.

[0024] The PMS severity evaluation device may further include providing a lifestyle improvement plan corresponding to the determined severity of PMS in the processing unit 13. In such a PMS severity evaluation device, the memory unit 12 further stores a correspondence relationship between the severity of PMS of the subject and lifestyle improvements corresponding to the severity of PMS; the processing unit 13 determines a lifestyle improvement plan corresponding to the severity of PMS from the correspondence relationship between the determined severity of PMS of the subject and the severity of PMS stored in the memory unit 12 and the lifestyle improvement plan corresponding to the severity of PMS; and the output unit 14 outputs the determined lifestyle improvement plan. The lifestyle improvement may be at least one selected from the group consisting of prescription drugs such as diuretics and antidepressants, over-the-counter drugs such as painkillers and Chinese herbal medicines, cosmetics for improving equol, vitamin B6, stratum corneum moisture content, skin barrier function, redness, and dullness, supplements, recommended food (nutrients, etc.), stress management, exercise recommendations, sleep habits, smoking cessation, and drinking less. For example, a subject whose skin condition is assessed as poor may be provided with information on skin care to improve their skin condition. Based on such skin care information, information on cosmetics, quasi-drugs, or pharmaceuticals suited to their skin condition may be provided, or cosmetics, quasi-drugs, or pharmaceuticals suited to their skin condition may be provided.

[0025] The processing unit 13 determines the severity of premenstrual syndrome by reading out the correspondence between the amount of hippuric acid and the severity of premenstrual syndrome stored in the memory unit 12, and determining the severity of premenstrual syndrome from the amount of hippuric acid input from the input unit 11 and the correspondence. If the correspondence is a correspondence table, the severity of premenstrual syndrome can be determined by reading out the severity of premenstrual syndrome corresponding to the amount of hippuric acid from the correspondence table. If the correspondence is a correlation equation, the numerical value for the severity of premenstrual syndrome can be determined by substituting the amount of hippuric acid into the correlation equation. If the correspondence is a correspondence between one or more thresholds and the severity of premenstrual syndrome, the severity of premenstrual syndrome can be determined by comparing with each threshold. The determined severity of premenstrual syndrome may be stored in the memory unit 12, or output from the memory unit 12 or directly from the processing unit 13 via the output unit 14.

[0026] In another embodiment, the PMS severity evaluation device can use a learning unit 15 that has been pre-trained using information on the amount of hippuric acid and information on the severity of PMS as training data when determining the severity of PMS. The learning unit 15 has been pre-trained to output the severity of PMS when data including the amount of hippuric acid is input. The PMS severity evaluation device specifically includes the following: an input unit 11 that inputs data including the amount of hippuric acid; a learning unit 15 that has been pre-trained using information on the amount of hippuric acid and information on the severity of PMS as training data, and that outputs the severity of PMS when data including the amount of hippuric acid is input from the input unit 11; and an output unit 14 that outputs the severity of PMS for the subject. Such a premenstrual syndrome severity evaluation device may further include a processing unit 13 and a memory unit 12, and the processing unit 13 may control input of data containing the amount of hippuric acid input from the input unit 11 to the learning unit 15, and control output of the severity of premenstrual syndrome output by the learning unit 15 from the output unit 14. The processing unit 13 may also perform pre-adjustment of the input hippuric acid data. As an example, the data containing the amount of hippuric acid input from the input unit 11 may be the target hippuric acid data itself, and in that case, the processing unit 13 may perform a step of extracting the amount of hippuric acid from the input hippuric acid data. The memory unit 12 may temporarily store the data containing hippuric acid input from the input unit 11 and the severity of premenstrual syndrome output by the learning unit 15.

[0027] The input unit 11 includes an interface. The interface may be connected to, for example, an operation unit such as a keyboard or a mouse, a communication unit such as a LAN or a port, or an external storage device such as a CD-ROM, a DVD-ROM, a BD-ROM, or a memory stick. Data including the amount of hippuric acid may be input via the operation unit. Furthermore, instructions for processing in the processing unit 13 can be given from the input unit 11 via the operation unit.

[0028] The storage unit 12 may include a memory device such as RAM, ROM, or flash memory, a fixed disk device such as a hard disk drive, or a portable storage device such as a flexible disk or optical disk. The storage unit 12 may also store data and instructions input from the input unit 11. The storage unit 12 stores a correspondence relationship between the amount of hippuric acid and the severity of premenstrual syndrome. Specifically, the correspondence relationship between the amount of hippuric acid and the severity of premenstrual syndrome may be stored as a correspondence table, graph, correlation equation, or threshold value. The storage unit 12 may store the results of the arithmetic processing performed by the processing unit 13, as well as programs and databases used for various computer processes, and may also store the program of the learning unit 15. The computer program may be installed from a computer-readable recording medium such as a CD-ROM or DVD-ROM, or via the Internet. The computer program is installed in the storage unit 12 using a known setup program or the like.

[0029] The processing unit 13 executes various types of arithmetic processing in accordance with the programs stored in the storage unit 12. The arithmetic processing is performed by a central processing unit (CPU) included in the processing unit 13. This CPU includes functional modules that control the input unit 11, the storage unit 12, the learning unit 15, and the output unit 14, and is capable of performing various types of control. Each of these units may be composed of an independent integrated circuit, microprocessor, firmware, or the like. Information generated after each process by the processing unit 13 may be temporarily stored in the storage unit 12, or may be used directly in the next process.

[0030] The output unit 14 is configured to output the severity of premenstrual syndrome generated by performing arithmetic processing in the processing unit 13. The output unit 14 may be an output means such as a display device such as a liquid crystal display that directly displays the results of the arithmetic processing, or a printer, or may be an interface unit for outputting to an external storage device or via a network.

[0031] The learning unit 15 uses known machine learning techniques, such as deep learning, to learn the relationship between input data containing hippuric acid levels and information about the severity of premenstrual syndrome at that time. Information about hippuric acid levels and information about the severity of premenstrual syndrome at that time can be obtained for various subjects, and the learning unit 15 can be trained using this data. Deep learning is machine learning using a multilayer neural network consisting of an input layer, an intermediate layer, and an output layer. A feature vector of the detection information is input to each node in the input layer. Each node in the intermediate layer outputs the sum of values ​​obtained by multiplying each feature vector output from each node in the input layer by a weight, and the output layer outputs the sum of values ​​obtained by multiplying each feature vector output from each node in the intermediate layer by a weight. The learning unit 15 adjusts each weight while learning to minimize the difference between the output value from the output layer and the information about the amount of hippuric acid. The input data input to the learning unit 15 is input data about the amount of hippuric acid.

[0032] [Premenstrual syndrome severity evaluation system] The premenstrual syndrome severity evaluation device 10 of the present invention may exist on a network and may constitute a premenstrual syndrome severity evaluation system including the premenstrual syndrome severity evaluation device 10. The premenstrual syndrome severity evaluation system is configured so that hippuric acid data is input via the network to the input unit 11 of the premenstrual syndrome severity evaluation device 10; and the determined severity of premenstrual syndrome is output via the network from the output unit 14. Such a premenstrual syndrome severity evaluation system may further include a terminal device 30 and / or a hippuric acid analyzer 40 connected via the network. That is, the premenstrual syndrome severity evaluation device 10 may exist on a server, and the input unit 11 and the output unit 14 may be connected to the network via their respective interface units. Furthermore, the learning unit 15 used by the premenstrual syndrome severity evaluation device 10 may also be located externally via a server or the like, and the severity of premenstrual syndrome may be evaluated via communication.

[0033] The hippuric acid analyzer 40 includes the following: a hippuric acid analysis unit; and an output unit, and data on the hippuric acid analysis results can be output via the output unit. The hippuric acid analysis data thus output may be provided to the premenstrual syndrome severity evaluation device via a network or directly. The hippuric acid analyzer 40 may be any device capable of analyzing hippuric acid in a sample, and a chromatography device, particularly an HPLC device, may be used.

[0034] The network-connected terminal device 30 may include: a network connection unit connected to the premenstrual syndrome severity evaluation device; and a terminal output unit outputting, via the network connection unit, at least one selected from the group consisting of the severity of premenstrual syndrome of the subject output from the output unit 14 of the premenstrual syndrome severity evaluation device and lifestyle improvement suggestions according to the severity of premenstrual syndrome. Data on the hippuric acid analysis results may be input to the premenstrual syndrome severity evaluation device via the network connection unit.

[0035] Another aspect of the present invention may relate to a program for causing the premenstrual syndrome severity evaluation device 10 to perform the above-mentioned processes. Such a program includes the following instructions to the processing unit 13: read input data including the amount of hippuric acid input from the input unit 11, read the correspondence between the amount of hippuric acid and the severity of premenstrual syndrome stored in the memory unit 12, determine the severity of premenstrual syndrome from the input data, the correspondence between the amount of hippuric acid, and the severity of premenstrual syndrome, and output the determined skin condition to the output unit 14. Instead of the step of causing the processing unit 13 to determine the severity of premenstrual syndrome from the correspondence between the amount of hippuric acid and the severity of premenstrual syndrome, the program may input the input data regarding the amount of hippuric acid to a learning unit 15 that has been pre-trained to output the severity of premenstrual syndrome when the input data regarding the amount of hippuric acid is input, thereby determining the severity of premenstrual syndrome.

[0036] All documents mentioned herein are incorporated by reference in their entirety.

[0037] The following examples of the present invention are for illustrative purposes only and do not limit the technical scope of the present invention. The technical scope of the present invention is limited only by the claims. The present invention may be modified, for example, by adding, deleting, or substituting components of the present invention, provided that the modifications do not depart from the spirit of the present invention.

[0038] Healthy women (aged 20-45 years) who were aware that they had premenstrual syndrome (PMS) were given a PMS questionnaire and given urine samples to clarify the relationship between PMS symptoms and hippuric acid levels. As shown in Figure 1, urine samples were collected and the PMS questionnaire was administered on the same day during the follicular phase test (5-10 days after the start of menstruation, when menstruation has ended and PMS symptoms have disappeared) and the luteal phase test (5 days before the start of the next menstruation, when PMS symptoms are present). The PMS questionnaire was administered according to the modified MDQ (Menstrual Distress Questionnaire). The revised MDQ was developed by Moos (Moos, RH: The Development of a Menstrual Distress Questionnaire. Psychosomatic Medicine 30: 853-869, 1968), translated by Akiyama et al. (Akiyama Akiyo, Kayashima Eko, "The Influence of the Menstrual Cycle on the Mind and Body as Seen in the MDT (Mirror Drawing Test)", Journal of the Four Universities Nursing Research Association 2(2): 61-66, 1979), and adapted for Japanese use. The Japanese version of the "Menstrual Distress Questionnaire (MDQ)" measures both mental and physical complaints associated with the menstrual cycle. The revised MDQ consists of 54 items, including 7 symptoms commonly associated with PMS (premenstrual syndrome) added by Odagawa et al. (Odagawa Hiroko, Shirato Nahoko et al.: A Study on Menstrual Distress Symptoms in Adolescent Girls Using MDQ Scores. Showa Medical Association Journal 68(3): 151-161, 2008). Subjects were considered to have PMS if their modified MDQ score was 103 or higher.

[0039] The relationship between urinary hippuric acid levels and the severity of PMS is shown in Figures 2 and 3. Figure 3 shows that when a subject is in the luteal phase, the higher the hippuric acid level, the lower the modified MDQ (mMDQ) score and the milder the severity of PMS. Figure 3 also shows that as a subject's hippuric acid level increases from the follicular phase to the luteal phase, the lower the modified MDQ score and the milder the severity of premenstrual syndrome.

[0040] Figure 4 shows hippuric acid levels in subjects diagnosed with PMS (mMDQ score ≥ 103) and subjects not diagnosed with PMS (mMDQ < 103) during the luteal phase. The mean luteal phase hippuric acid concentration in subjects diagnosed with PMS with a mMDQ score ≥ 103 was approximately 200 mg / L or less. Figure 5 shows the change in hippuric acid levels from the follicular phase to the luteal phase in subjects diagnosed with PMS (mMDQ score ≥ 103) and subjects not diagnosed with PMS (mMDQ < 103). The mean delta creatinine-corrected hippuric acid concentration (luteal phase - follicular phase) in subjects diagnosed with PMS with a mMDQ score ≥ 103 was approximately 0.3 or less.

Claims

1. A method for evaluating the severity of premenstrual syndrome in a subject, using hippuric acid in a sample derived from the subject as an indicator.

2. The method according to claim 1, comprising a step of quantifying hippuric acid.

3. (1) In the subject whose menstrual cycle is in the luteal phase, if the value of hippuric acid is significantly lower than the value of the group with mild premenstrual syndrome, it serves as an indicator of severe premenstrual syndrome; (2) In the subject whose menstrual cycle is in the period from the follicular phase to the luteal phase, if the value of hippuric acid rises during that period for the subject, it serves as an indicator of mild premenstrual syndrome. The method according to claim 1 or 2.

4. The method according to any one of claims 1 to 3, wherein the sample is urine.

5. The method according to any one of claims 1 to 4, wherein the exacerbation of the severity of premenstrual syndrome is caused by an increase in oxidative stress in the body.

6. A kit for evaluating the severity of premenstrual syndrome in a subject, comprising means for measuring hippuric acid in a sample derived from the subject.

7. The kit according to claim 6, which quantifies hippuric acid.

8. (1) In the subject whose menstrual cycle is in the luteal phase, if the value of hippuric acid is significantly lower than the value of the group with mild premenstrual syndrome, it serves as an indicator of severe premenstrual syndrome; (2) In the subject whose menstrual cycle is in the period from the follicular phase to the luteal phase, if the value of hippuric acid rises during that period for the subject, it serves as an indicator of mild premenstrual syndrome. The kit according to claim 6 or 7.

9. The kit according to any one of claims 6 to 8, wherein the sample is urine.

10. An apparatus for evaluating the severity of premenstrual syndrome, comprising an input unit for inputting data on the amount of hippuric acid in a sample derived from a subject, a storage unit for storing the relative relationship between the amount of hippuric acid and the severity of premenstrual syndrome, and an output unit for outputting the severity of premenstrual syndrome from the relative relationship.

11. The apparatus according to claim 10, further comprising a processing unit for determining the severity of premenstrual syndrome from the amount of hippuric acid in a sample derived from a subject and the relative relationship between the amount of hippuric acid stored in the storage unit and the severity of premenstrual syndrome.

12. The apparatus according to claim 10 or 11, comprising a step of quantifying hippuric acid.

13. (1) In the subject whose menstrual cycle is in the luteal phase, if the value of hippuric acid is significantly lower than the value in the group with mild premenstrual syndrome severity, it serves as an indicator of severe premenstrual syndrome severity. (2) In the subject whose menstrual cycle is in the period from the follicular phase to the luteal phase, if the value of hippuric acid increases during that period for the subject, it serves as an indicator of mild premenstrual syndrome severity. The apparatus according to any one of claims 10 to 12.

14. The apparatus according to any one of claims 10 to 13, wherein the sample is urine.

15. The apparatus according to any one of claims 10 to 14, wherein the exacerbation of premenstrual syndrome severity is caused by an increase in oxidative stress in the body.

16. The premenstrual syndrome severity evaluation apparatus provides a life improvement plan according to the severity of premenstrual syndrome based on the determined severity of premenstrual syndrome in the subject, where: the storage unit further stores the correspondence between the severity of premenstrual syndrome in the subject and the life improvement according to the severity of premenstrual syndrome; the processing unit determines a life improvement plan according to the severity of premenstrual syndrome from the correspondence between the determined severity of premenstrual syndrome in the subject, the correspondence between the severity of premenstrual syndrome in the subject stored in the storage unit and the life improvement according to the severity of premenstrual syndrome; the output unit outputs the determined life improvement plan. The apparatus according to any one of claims 10 to 15, including this.

17. The apparatus according to claim 16, wherein the life improvement plan is at least one selected from the group consisting of intake of components for alleviating premenstrual syndrome severity, taking pills, encouraging exercise, smoking cessation, alcohol abstinence, and antioxidant supplements.

18. A system including the apparatus according to any one of claims 10 to 17, wherein the apparatus is connected to a network, data on the value of hippuric acid in a sample from a subject is input via the network at the input unit; the severity of premenstrual syndrome determined is output via the network from the output unit. The system including this.

19. Further including a terminal device connected to a network, the terminal device includes the following: A network connection part connected to the device; A terminal output part that outputs at least one selected from the group consisting of the severity of premenstrual syndrome of a target output from the output part of the device and a life improvement plan according to the severity of premenstrual syndrome via the network connection part. The system according to claim 18.

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