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Physiology, Menarche

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Last Update: April 25, 2019.

Introduction

Menarche is the occurrence of a first menstrual period in the female adolescent. Menstruation is the monthly shedding of the functional layer of the uterine endometrial lining that occurs when ovulation is not followed by fertilization. It occurs approximately every 28 days, with a range from every 21 to every 45 days. The average age of onset of menarche is 12.4 years. Most menstrual periods last between 3 and 7 days, and menses that last more than 10 days is considered abnormal. Menarche signals maturation of the adolescent female body. It commonly is associated with the ability to ovulate and reproduce. However, the appearance of menarche does not guarantee either ovulation or fertility.[1][2][3]

Issues of Concern

Menarche occurs in the setting of a maturing hypothalamic-pituitary-ovarian (HPO) axis. It relies on the following processes: normal hypothalamic and pituitary function, normal female reproductive anatomy, normal nutrition, and the general absence of other intervening chronic illness. It is a marker of normal female reproductive health and wellness. Most females recognize menarche as their body’s critical declaration of fertility. The absence of normal menstrual periods, not related to pregnancy, is called amenorrhea. Primary amenorrhea is the complete absence of any menstruation by 15 years of age. Secondary amenorrhea is the cessation of menstruation for 3 months or more after it has started. In the first 2 to 3 years after the initial onset of menses, it is common for irregular cycles to occur, with adolescents often having several months of missed menses. Many of these irregular cycles may be nonovulatory due to poor early regulation of the hormonal interactions between hypothalamic, pituitary, and gonadal hormones. Tracking menstruation on a paper calendar or using a smartphone app can be helpful in determining if menstrual periods are becoming more regular for adolescents and also for predicting when ovulation is most likely to occur. The information can be used for both pregnancy planning and pregnancy prevention.[4][5][6][7]

Development

The average age of menarche is 12.4 years but varies with ethnic or racial background. This age has been decreasing over the past 100 years and is most often attributed to improvements in child and adolescent nutrition. Exogenous hormones in the diet also may contribute to this earlier initiation of menarche. The average age of menarche for Caucasians generally is slightly later compared to other races. Menarche most commonly occurs in sexual maturity rating (SMR), or Tanner stage, IV. It is abnormal for menarche to occur before the appearance of secondary sexual development. Sexual abuse, genital trauma, tumors, or bleeding disorders should strongly be considered in the differential diagnosis of females who are prepubertal and experience vaginal bleeding. Menarche generally is considered early if it occurs before 9 years of age and late if it occurs at or after 15 years of age. Menarche is considered delayed if there is more than a 5-year lapse between the onset of breast development (SMR II breasts or breast buds) and the first menses. Menarche occurs during a time of puberty that is associated with rapid growth velocity. Typically, adolescent females who experience menarche are not ovulatory with every cycle in the first year. It is estimated that most will have ovulatory cycles within 5 years of menarche. Imperforate hymen is the most common congenital genital tract anomaly in females ranging from 1/1000 to 1/10,000 in prevalence. It can be noted at birth, as the estrogenized hymen in the newborn period often is readily apparent. The absence of a normal uterus or vagina, due to Mullerian agenesis or Mayer-Rokitansky-Kuster-Hauser syndrome, has an incidence of approximately 1/4500 females and often is not diagnosed until a patient presents with the absence of menarche. Other complex hormonal abnormalities such as androgen insensitivity syndrome can present with external female development and primary amenorrhea. Abnormal development of female gonads due to Turner syndrome also can lead to ovarian agenesis and absent menses.[8][9][10]

Organ Systems Involved

Menarche is the result of complex interactions between the hypothalamic, pituitary, and ovarian hormones. It also can be affected by thyroid, adrenal, and pancreatic hormones. Thyroid hormones are necessary for normal menses, and their deficiency or excess can inhibit menarche or lead to abnormalities in existing menstrual patterns. Abnormally elevated adrenal androgens or insulin can affect normal ovarian estrogen production, as well as decrease the normal pituitary production of luteinizing hormone. Low adiposity can inhibit normal menarche, and it is estimated that a minimum body fat of 17% is necessary for menarche, with 22% body fat necessary for maintaining normal menses. The hormone leptin appears to have a role in the maintenance of normal menstrual cycles as well. Stress and obesity appear to be predictors of early menarche.

Function

Normal menstruation is an indicator of fertility and reproductive ability. Its absence should signal the provider to evaluate for pathology.

Mechanism

Pulsatile hypothalamic production of gonadotropin-releasing hormone (GnRH) at puberty stimulates the pituitary production of follicle stimulating hormone (FSH) and luteinizing hormone (LH). This pulsatile secretion pattern appears to be necessary as continuous secretion of GnRH, or its synthetic analogs, inhibits pituitary production of FSH and LH and delays menarche. This can be used medically to delay puberty in children with precocious puberty. FSH and LH, in turn, stimulate an increase in ovarian production of estrogens, primarily estradiol, and androgens. Estradiol promotes maturation of ovarian follicles, with one follicle gaining dominance during each menstrual cycle. Increasing levels of estrogens stimulate uterine endometrial proliferation and eventually cause a surge of LH production by the pituitary. This LH surge causes ovulation or rupture of the dominant ovarian follicle.

Related Testing

In patients with normal anatomy and delayed development, evaluation of ovarian and pituitary hormones, including androgens, can be helpful in making a diagnosis. Pituitary tumors, most often adenomas, may cause amenorrhea and can be associated with elevated prolactin levels and galactorrhea, as well as physical findings that may include breast discharge, headaches, and vision changes. In primary amenorrhea, estradiol levels are helpful in measuring ovarian function. If estradiol levels are low, reflexive testing of FSH and LH will differentiate between primary ovarian failure (FSH/LH elevated) and secondary ovarian failure (FSH/LH low or unmeasurable, pituitary failure). If there is evidence of hirsutism or acne on an exam, testing of androgen levels, including free and total testosterone, DHEA-S, and 17-hydroxyprogesterone, will help to rule out androgen-secreting tumors and congenital adrenal hyperplasia as a cause. They also can help to confirm a diagnosis of polycystic ovary syndrome (PCOS). It should be pointed out that the absence of menarche can occur due to pregnancy, and ruling out pregnancy is essential in the evaluation.

Pathophysiology

PCOS is a common condition that affects 6% to 8% of the female population. It involves dysregulation of the HPO axis and often causes amenorrhea. Complications of PCOS include obesity, diabetes mellitus type 2, and infertility. It is treatable, but not curable. The most common genetic syndrome associated with amenorrhea in adolescent females is Turner syndrome.[11]

In healthy, mature females who are not on hormonal therapy, it is recommended that they have a minimum of three to four menstrual periods a year to promote a healthy endometrium and decrease their risk for endometrial cancer.

Clinical Significance

Anatomical problems leading to amenorrhea usually can be diagnosed by a thorough history and careful visual exam of external genitalia and manual exam of the reproductive organs of the adolescent female patient. By law, it is important that clinicians take a history in private and maintain confidentiality whenever possible. It also is important to explain the exam in detail and to provide a chaperone during the exam, especially when the practitioner is male. Menarche can be delayed in adolescents with very low body mass due to starvation, malabsorption, or because of an eating disorder such as anorexia nervosa. Menarche can be delayed in normally developing females due to abnormalities of the female genitourinary tract. Females with an imperforate hymen may present with delayed menarche and often will have a history of recurrent cyclic abdominal or pelvic pain. On exam, they often have a bulging and blueish colored hymen. A manual exam of the reproductive organs may reveal a blind vaginal pouch in patients with Mullerian agenesis. Ultrasound imaging can be used to confirm anatomic problems, or ultrasound can be used in patients who are unwilling to have a manual exam of their internal reproductive organs. Treatment for persistent amenorrhea depends on the etiology.[12]

Questions

To access free multiple choice questions on this topic, click here.

References

1.
Rosner J, Sarao MS. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jan 9, 2019. Physiology, Female Reproduction. [PubMed: 30725817]
2.
Petry CJ, Ong KK, Hughes IA, Acerini CL, Dunger DB. Age at Menarche and Blood Pressure in Pregnancy. Pregnancy Hypertens. 2019 Jan;15:134-140. [PMC free article: PMC6352955] [PubMed: 30713829]
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Zhang Z, Hu X, Yang C, Chen X. Early age at menarche is associated with insulin resistance: a systemic review and meta-analysis. Postgrad Med. 2019 Mar;131(2):144-150. [PubMed: 30560708]
4.
Kendel NE, Haamid FW, Christian-Rancy M, O'Brien SH. Characterizing adolescents with heavy menstrual bleeding and generalized joint hypermobility. Pediatr Blood Cancer. 2019 Jun;66(6):e27675. [PubMed: 30803134]
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Carlson LJ, Shaw ND. Development of Ovulatory Menstrual Cycles in Adolescent Girls. J Pediatr Adolesc Gynecol. 2019 Feb 14; [PubMed: 30772499]
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Coast E, Lattof SR, Strong J. Puberty and menstruation knowledge among young adolescents in low- and middle-income countries: a scoping review. Int J Public Health. 2019 Mar;64(2):293-304. [PMC free article: PMC6439145] [PubMed: 30740629]
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Marnach ML, Laughlin-Tommaso SK. Evaluation and Management of Abnormal Uterine Bleeding. Mayo Clin. Proc. 2019 Feb;94(2):326-335. [PubMed: 30711128]
8.
Dunneram Y, Greenwood DC, Cade JE. Diet, menopause and the risk of ovarian, endometrial and breast cancer. Proc Nutr Soc. 2019 Feb 01;:1-11. [PubMed: 30706844]
9.
De Sanctis V, Rigon F, Bernasconi S, Bianchin L, Bona G, Bozzola M, Buzi F, De Sanctis C, Tonini G, Radetti G, Perissinotto E. Age at Menarche and Menstrual Abnormalities in Adolescence: Does it Matter? The Evidence from a Large Survey among Italian Secondary Schoolgirls. Indian J Pediatr. 2019 Jan;86(Suppl 1):34-41. [PubMed: 30628040]
10.
Calthorpe L, Brage S, Ong KK. Systematic review and meta-analysis of the association between childhood physical activity and age at menarche. Acta Paediatr. 2018 Dec 27; [PubMed: 30588652]
11.
Kamboj MK, Bonny AE. Polycystic ovary syndrome in adolescence: diagnostic and therapeutic strategies. Transl Pediatr. 2017 Oct;6(4):248-255. [PMC free article: PMC5682369] [PubMed: 29184806]
12.
Zhang C. The roles of different stem cells on premature ovarian failure. Curr Stem Cell Res Ther. 2019 Mar 14; [PubMed: 30868961]
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Bookshelf ID: NBK470216PMID: 29261991

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