Irregular menstrual cycles

Overview

Women who have menstrual disorders, such as irregular menstruation, menorrhagia, amenorrhea, dysmenorrhea, and premenstrual symptoms, have much worse health. Furthermore, the menstrual cycle is an indicator of women's overall health. The reproductive health of a mother may have an impact on the health of her children after delivery.

Menstrual disorders are regarded as major health indicators among working women since an aberrant menstrual cycle is linked to health-related anxiety and unhappiness. Furthermore, irregular menstruation has a detrimental impact on workplace efficiency.

What are Irregular menstrual cycles?

Menstrual cycle disruptions are caused by hormonal abnormalities caused by exposure to:

• Environmental stress, e.g., changes in energy balance (excessive physical activity, low energy intake),
• Exposure to pollutants (present in polluted air and tobacco smoke), and 
• Psychosocial stress.

Menstrual irregularity, defined as an irregular menstrual cycle, is a kind of abnormal menstruation caused by a variety of factors, including:

• The presence of a disease (i.e., endometriosis, type 2 diabetes mellitus, etc.), 
• Medication use (i.e., drug-treated depression, antiandrogens, etc.), 
• Underweight or obesity,
• Smoking habit, and
• Reproductive factors (age at menarche, parity, etc.). 

Epidemiology

Irregular menstruation can have a variety of health consequences and is an indication of women's health. Depending on age, employment, and country of residence, the prevalence of irregular menstruation ranges from 5% to 35.6 percent. In particular, 14.3 percent of adult Korean women have menstruation irregularity; while this figure is not excessive, it is growing by 0.4 percent every year.

Irregular menstruation can be caused by hormonal imbalances and stress, both of which operate as health indicators in women and as mediators of other health indicators. In addition to physiological issues, irregular menstruation is linked to mental health disorders such as depression.

According to Statistics Korea 2015, women have begun to enter the labor field at a later age as their educational level has grown. Furthermore, they marry for the first time and have their first kid at the ages of 30 and 31.5, respectively. Various menstruation difficulties, such as amenorrhea, monthly discomfort, and abnormal uterine flow, are more common in women in their 20s–30s, and the prevalence of these issues continues to rise after the age of 30.

Menstrual irregularity causes

Menstrual problems in teenagers can manifest as abnormal uterine bleeding (AUB). AUB, in its broadest sense, comprises the following:

• Absence of bleeding
• Irregular bleeding
• Abnormally heavy bleeding
• Bleeding in between periods

• Primary amenorrhea

Amenorrhea, or irregular menstruation, can be primary or secondary. Primary amenorrhea can be either

1. The lack of menstruation by the age of 15 years (or within 3 years of thelarche) with otherwise normal pubertal development or
2. The lack of secondary sexual characteristics by the age of 13 years. 

• Secondary amenorrhea is defined as a 6-month absence from menstruation, while it is unusual for teenagers to miss more than three months.

Ovarian insufficiency, müllerian agenesis, and hypogonadotopic hypogonadism are the most prevalent causes of primary amenorrhea. Ovulation and intercourse can occur before the commencement of menarche; therefore, pregnancy must also be considered.

There are several classifications for the causes of primary amenorrhea. One technique is to categorize the reasons based on gonadotropin levels and ovarian hormone production, as shown below:

• Hypogonadotropic hypogonadism-Anorexia; stress- and exercise induced hypogonadism; GnRH deficiency; hyperprolactinemia; hypopituitarism
• Eugonadotropic eugonadism-Pregnancy; imperforate hymen; Asherman's syndrome; Mullerian agenesis; polycystic ovary syndrome (PCOS)
• Hypergonadotropic hypogonadism-Ovarian dysgenesis; ovarian insufficiency; complete androgen insensitivity syndrome; congenital adrenal hyperplasia

Abnormal uterine bleeding

AUB is determined by four factors, according to the International Federation of Gynecology and Obstetrics (FIGO) system: frequency, regularity, duration, and volume. This system's 2018 version incorporates intermenstrual hemorrhage. AUB causes can be categorized using the PALM-COEIN system, which states:

• The acronym PALM represents structural causes (polyp, adenomyosis, leiomyoma, malignancy, and hyperplasia) and
• The acronym COEIN represents nonstructural causes (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not otherwise classified). 

Ovulatory dysfunction

The most prevalent cause of AUB in teenagers is ovulatory dysfunction. For the first several years after menarche, cycles are not regularly ovulatory, especially if menarche occurs at a later age. The most prevalent reason of irregular menstrual periods at this time is HPO axis immaturity, although other etiologies, such as pregnancy, PCOS, hypothyroidism, hyperprolactinemia, and functional hypothalamic dysfunction, should be explored.

An oocyte is not released during anovulatory cycles, and progesterone is not generated in the absence of the development of a corpus luteum. Endometrial proliferation occurs as a result of unopposed estrogen and weak blood vessels. The endometrium develops abnormally, resulting in unexpected, erratic, and occasionally excessive and persistent bleeding.

Polycystic ovary syndrome

PCOS is the most prevalent endocrine condition, accounting for 6-10% of all cases. It is also the most prevalent cause of hyperandrogenism-related irregular menstrual flow, oligomenorrhea, or amenorrhea.

The National Institute of Health, the Rotterdam Consensus Criteria, and the Androgen Excess Society have all developed diagnostic criteria for PCOS. They all incorporate two of the following three requirements in some combination:

• Hyperandrogenism (either clinical or laboratory)
• Oligomenorrhea or amenorrhea
• Polycystic ovaries on pelvic ultrasonography (US)

Obesity is typically associated with PCOS because insulin resistance plays a role in the disease's basic pathogenesis, yet up to 20% of individuals with PCOS are not fat. Metabolic syndrome is especially frequent among PCOS teenagers, putting them at a higher risk for cardiovascular disease and diabetes.

Endometrial cancer

Endometrial cancer, though uncommon in women under the age of 40, should be considered in teenagers with irregular menstruation. The most prevalent symptom was irregular menstruation.

Menorrhagia 

Menorrhagia is defined as blood loss greater than 80 mL or bleeding lasting more than 7 days each menstrual cycle. Because objective testing of blood loss through the alkaline hematin technique is time-consuming, AUB-HMB is frequently classified subjectively as excessive menstrual bleeding, despite the fact that subjective evaluations of blood loss have been shown to be mainly erroneous.

The most prevalent causes of bleeding disorders in adolescents are von Willebrand disease, factor deficiencies, and platelet abnormalities, with von Willebrand disease being the most common hereditary bleeding disorder. 

Intermenstrual bleeding

Intermenstrual bleeding (IMB), also known as metrorrhagia, is defined as bleeding that occurs between periods. The following are common reasons among adolescents:

• Pregnancy
• STIs
• Latrogenic etiologies from administration of exogenous steroids, including oral contraceptive pills

Pregnancy, including ectopic pregnancy, can cause uterine bleeding or amenorrhea.

Pathophysiology

Puberty involves the maturing of the neuroendocrine system, which takes several phases to complete. The hypothalamus starts secreting gonadotropin-releasing hormone (GnRH), and as it does, pituitary gonadotropins including luteinizing hormone [LH] and follicle-stimulating hormone [FSH], as well as ovarian follicles, become more susceptible to stimulation.

Increased GnRH pulsatility causes gonadotropin release, which leads to the selection of a dominant follicle. As the follicle develops, it releases estrogen, which offers positive feedback to the gonadotropins, causing an LH surge and, ultimately, ovulation. During ovulatory menstrual cycles, the dominant follicle secretes estradiol, causing the endometrium to develop and prepare for prospective implantation.

As the granulosa cells become luteinized after ovulation, a corpus luteum emerges. The corpus luteum secretes progesterone, which helps the endometrium become more stable for prospective implantation. Without the implantation of an embryo, the corpus luteum involutes, resulting in decreased progesterone and estradiol levels and, as a result, shedding of the endometrium as it loses its blood supply.

Menarche and the menstrual cycle may not occur or may occur irregularly, resulting in the absence or atypical menses if any of the preceding processes is interrupted.

The median age of menarche in the United States is 12.43 years, with only 10% of girls menstruation at 11 years and 90% by 13.75 years. Non-Hispanic blacks reach menarche at a younger age, 12.06 years, compared to 12.55 years for non-Hispanic whites.

When females reach Tanner stage IV breast and pubic hair growth, and menarche occurs. The usual time between the formation of breast buds and the commencement of menarche is 2-3 years. Anovulatory cycles are more prevalent in the early years after menarche, accounting for up to half of all cycles. Nonetheless, most cycles still last between 2 and 7 days and last between 21 and 45 days.

The age at menarche is related to the amount of time required to attain regular ovulatory cycles. Menarche at a younger age is related with more than 50% ovulatory cycles after 1 year, but menarche at a later age is not connected with completely ovulatory cycles for 8-12 years.

Finally, during a typical menstrual cycle, a woman will shed 30-40 mL of blood or use three to six pads or tampons every day. A loss of more than 80 mL of blood or bleeding that lasts more than 7 days indicates irregular menstrual flow.

Irregular menstrual cycle Diagnosis

• Primary amenorrhea

The laboratory workup for primary amenorrhea is determined by the history and physical examination results. If a blind-ending vaginal pouch is observed, testosterone levels and karyotyping are recommended to differentiate between müllerian agenesis and total androgen insensitivity syndrome.

If a uterus is present, a pregnancy test and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, thyroid-stimulating hormone (TSH), and prolactin are performed. Estradiol and progesterone levels must be low in order to interpret FSH and LH test findings. In young women who do not have menstruation, it is occasionally essential to take weekly estradiol and progesterone levels until they suggest that the patient is in the early follicular phase, and then take FSH and LH levels.

If FSH levels are elevated, primary hypogonadism is expected, and karyotyping should be undertaken to rule out Turner syndrome (45X) or Swyer syndrome (46, XY). If the FSH is low or normal, the etiology is most likely hypothalamic, and additional workup may involve head imaging if no clear explanation (ie, stress- or exercise-induced hypothalamic dysfunction) is found.

If the prolactin level is elevated, it is critical to ensure that it was taken when fasting and without any recent nipple stimulation; if it was not, the test may need to be redone. If the prolactin level remains excessive and there has been no recent drug usage, including psychiatric medicines, to explain the spike, MRI of the pituitary should be conducted to rule out a pituitary microadenoma or adenoma.

Serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxyprogesterone (17-OHP) levels should be examined if there are indicators of hyperandrogenism to rule out an ovarian or adrenal tumor or congenital adrenal hyperplasia.

• Abnormal uterine bleeding

A pregnancy test, a complete blood count (CBC), TSH levels, testing for gonorrhea and chlamydia, and screening for bleeding disorders should all be included in a laboratory assessment for abnormal uterine bleeding (AUB). Testing for HIV, syphilis, and hepatitis B and C should also be explored in high-risk patients.

Hormone levels (e.g., estradiol, FSH, LH, and prolactin) may be measured in patients with irregular bleeding patterns. Again, these values should be collected in the early follicular phase for accurate interpretation; if menstruation is irregular, weekly estradiol and progesterone levels can be obtained until they are sufficiently low, at which point LH and FSH can be added. If there is worry about insulin resistance or metabolic abnormalities, a 2-hour glucose tolerance test, as well as fasting lipid values, should be performed.

If androgen excess is suspected, or as part of an initial screening, free and total testosterone levels, DHEA-S, and 17-OHP should be measured. Screening for bleeding disorders involves a complete blood count (CBC) with platelets, coagulation tests, and, if von Willebrand disease is suspected, von Willebrand-ristocetin cofactor activity, von Willebrand factor antigen, and factor VIII level.

• Imaging Studies

Diagnostic imaging for primary amenorrhea, like laboratory workup, is based on the history and physical examination results.

Transvaginal ultrasonography is commonly used to begin imaging tests for AUB (US). Imaging is not required in all individuals, but it is indicated if aberrant findings on physical examination (for example, an enlarged uterus) are identified or if symptoms persist despite therapy in a patient with normal physical findings. Further testing may involve hysterosonography or hysteroscopy, and some people may require laparoscopy, particularly if endometriosis is suspected.

Management

Having irregular periods is common and does not necessitate therapy. Irregularity caused by puberty, perimenopause, or contraception does not usually necessitate therapy.

However, someone may want to speak with a doctor if:

• The abnormality persists and has no obvious reason.
• Period irregularities might be caused by a medicine or a medical issue.
• Irregular periods occur in conjunction with other symptoms such as pelvic discomfort.
• The individual wishes to become pregnant.

A doctor will be able to determine whether there is an underlying reason. The treatment will be determined by the cause of the abnormality.

The potential treatment recommendations may include:

• Hormone therapy: Birth control containing the hormones estrogen and progesterone can assist boost hormone levels, which helps offset the consequences of infertility. It can also help to make bleeding more regular and simpler to manage, as well as lower symptoms of disorders like PCOS, which may enhance the quality of life.
• Reaching a moderate weight: Menstruation can be affected by both a lack of body fat and an excess of body fat. Maintaining a healthy weight helps reduce insulin levels in persons with PCOS who have greater body weight. This results in reduced testosterone levels and an increased likelihood of ovulating.
• Nutritional therapy: A dietician can help people who desire to reduce or gain weight or who have an underlying disease that impacts their eating. They can assist a person in understanding the sort of food that will benefit their specific circumstances and promote hormone health.
• Mental health treatment: If irregular periods are caused by stress, worry, sadness, or an eating issue, a doctor may advise you to seek psychological help. For many, this generally entails seeing a psychologist for talk therapy. A multidisciplinary team will assist patients with eating issues through frequent treatment, nutritional counseling, and support groups. People who are severely underweight may require hospitalization.
• Additional medications: People who have irregular periods may benefit from certain drugs, depending on the underlying cause. For those with PCOS, a doctor may prescribe metformin. This is a type 2 diabetes insulin-lowering oral medication that can help assure ovulation and regular periods.

Conclusion 

Menstrual difficulties are fairly frequent in adolescence and can create a great deal of stress for both patients and their parents. The menstrual cycle varies greatly at this age, owing mostly to the immaturity of the hypothalamic-pituitary-ovarian (HPO) axis. Amenorrhea (either primary or secondary), abnormal uterine bleeding, and dysmenorrhea are all problems that must be evaluated carefully and logically.

The phrase primary amenorrhea refers to the absence of menarche, whereas secondary amenorrhea refers to the cessation of menstruation once it has begun. The presence of irregular, prolonged, or heavy abnormal uterine bleeding is one of the most pressing gynecological issues in adolescence, and the diagnosis of dysfunctional uterine bleeding should be used only after all other organic and structural causes of abnormal vaginal bleeding have been ruled out.

Dysmenorrhea, or painful menstruation, is the most common cause for a young girl to consult a gynecologist. It is classified as primary when there is no underlying organic illness and secondary when there is pelvic pathology. Appropriate and early patient care is required to reduce the likelihood of future difficulties with a woman's reproductive capabilities.

Early detection and treatment of menstrual abnormalities can help prevent the development of infertility and the complications of major conditions including congenital heart disease and osteoporosis. However, South Korean women have a poor impression of seeing a gynecologist and do not consider menstruation irregularity to be a serious health concern. Furthermore, many women believe that their symptoms will go away with time and are typically reluctant to seek therapy.