Oligo- and amenorrhea

A condition in which a woman has infrequent irregular menstruations is called oligomenorrhea, and the absence of menstruations is amenorrhea[1]. To understand the problem, firstly, knowledge of the normal menstrual cycle is required[2].

Normal menstrual cycle 

About once a month, females who have gone through puberty and haven’t reached menopause yet experience menstrual bleeding. It occurs because the thickened and rich in blood vessels, the uterus lining is shed when pregnancy doesn’t happen. Bleeding usually lasts for 3-8 days. 

The entire menstrual cycle is counted from the first day of one period to the beginning of the next. It has a duration typically between 21 and 35 days and includes several phases. 

The follicular phase starts on the first day of menstruation and ends with the beginning of ovulation. During this period, the pituitary gland releases follicle-stimulating hormone (FSH), contributing ovaries to produce follicles[3]. One of the follicles becomes dominant and houses a mature egg (when two follicles become dominant, it can lead to twins developing if eggs will be fertilized during this cycle)[4]. Estrogen level is increased, and consequently, the uterus lining becomes thicker. 

During the ovulation phase, hormone swings cause releasing of the mature egg (ovulation), which happens on about the 14th day of the menstrual cycle. After release, the egg enters the fallopian tube, where fertilization may occur if sperm are present. 

During the luteal phase, if fertilization has occurred, the corpus luteum produces progesterone, preventing the endometrial lining from being shed. If fertilization has not occurred, the corpus luteum disintegrates, and progesterone levels drop. 

But when something goes wrong, the menstrual cycle may become irregular. 

Diagnosing of oligo- and amenorrhea

It’s common for teenage girls or at postpartum to have irregular menstrual cycles. But they must become normal during the first two or three years. If your periods don’t occur for more than 35 days regularly or are absent, your doctor may diagnose oligomenorrhea. 

Causes

The etiology of oligo- and amenorrhea may vary. Some causes of its condition are divided into the following groups. 

Hypothalamic-pituitary failure

Irregular menstruations can be caused by hypogonadotrophic hypogonadism when FSH and luteinizing hormone (LH) concentrations decrease, and their levels don’t contribute to follicle development. The causes of this condition may be as follows:

  • hypophysectomy
  • radiotherapy for tumors of the pituitary gland
  • exercise-related amenorrhea in athletes and ballet dancers[5]  
  • weight-related amenorrhea, caused by a drastic loss of weight and dieting[6]  
  • stress-related amenorrhea
  • Kallmann’s syndrome – rare genetic disorders characterized by absent or partial puberty, hypogonadism associated with anosmia[7]. Lack of gonadotropin-releasing hormone (GnRH) secretion from hypothalamic neurons results in deficient pituitary LH and FSH release. 
  • Sheehan’s syndrome – postpartum hypopituitarism caused by necrosis of the pituitary gland as a result of massive bleeding during or after delivery

Hypothalamic-pituitary dysfunction

This group of dysfunction is caused by polycystic ovary syndrome, known as PCOS.  It is a group of symptoms that include cysts’ appearance in the ovaries, increased levels of male hormones, and menstrual irregularity[8]. PCOS etiology is associated with the extra production of androgens, which is 70% inherited. There are hypotheses about the exposure of the fetus to excess androgens.  Hyperandrogenism is connected with high testosterone concentrations, acne, and hirsutism. PCOS can be the cause of anovulation, and consequently, female infertility. This syndrome is also associated with obesity, cardiovascular risks, insulin resistance, etc.

Ovarian failure

It is the leading cause of oligo- and amenorrhea for about 10% of women. It is related to the dysfunction of ovaries, which don’t produce enough estrogens, and consequently, FSH becomes increased because of ovaries’ unresponsiveness to its concentrations. It may be based on the following conditions:

  • chromosomal abnormalities, such as Turners syndrome, when one X chromosome is absent, the stature is short, the neck is webbed, and ovaries are streak
  • autoimmune diseases
  • infections, like mums 
  • pelvic inflammation or surgery
  • chemotherapy or radiation 

Hyperprolactinemia

It is a condition associated with high concentrations of the hormone prolactin (PRL), which results in hypogonadism, galactorrhea, oligomenorrhea, and infertility[9]. 

The most frequent cause of hyperprolactinemia is a prolactinoma, a benign pituitary tumor producing prolactin[10]. Due to their size, these tumors are divided into microprolactinomas (<10 mm in diameter) and macroprolactinomas ( >10 mm in diameter). 

Hypothyroidism, the hypofunction of the thyroid gland, is known to be the other cause of hyperprolactinemia. The lack of thyroid hormones contributes to elevated thyroid-stimulating hormone (TSH) production, which is also a prolactin-releasing hormone. 

Prolonged stress and some medications, such as sedatives, anti-emetics, and oral contraceptives, are also thought to trigger hyperprolactinemia appearance. 

Outflow tract defects

These conditions include mechanical preventing of menstruations and are not related to ovulation disorders. The reasons include imperforate hymen, transverse vaginal septum, Asherman’s syndrome (intrauterine adhesions), cervical stenosis, and Mullerian abnormalities (uterine hypoplasia or absence).

References

  1. Riaz Y, Parekh U. Oligomenorrhea. StatPearls. Treasure Island (FL). 2021 Jan.
  2. Mihm M, Gangooly S, Muttukrishna S. The normal menstrual cycle in women. Anim Reprod Sci. 2011 Apr;124(3-4):229-36. doi: 10.1016/j.anireprosci.2010.08.030. 
  3. Baird DT, McNeilly AS. Gonadotrophic control of follicular development and function during the oestrous cycle of the ewe. J Reprod Fertil Suppl. 1981;30:119-33. PMID: 6300383. 
  4. Hall JG. Twinning. Lancet. 2003 Aug 30;362(9385):735-43. doi: 10.1016/S0140-6736(03)14237-7.
  5. Berz K, McCambridge T. Amenorrhea in the Female Athlete: What to Do and When to Worry. Pediatr Ann. 2016 Mar;45(3):e97-e102. doi: 10.3928/00904481-20160210-03. 
  6. Koebnick C, Strassner C, Hoffmann I, Leitzmann C. Consequences of a long-term raw food diet on body weight and menstruation: results of a questionnaire survey. Ann Nutr Metab. 1999;43(2):69-79. doi: 10.1159/000012770.
  7. J. Rohayem, M. Zitzmann, E. Nieschlag. Congenital Hypogonadotropic Hypogonadism and Kallmann’s Syndrome. Reference Module in Biomedical Sciences, Elsevier. 2015. ISBN 9780128012383, doi: 10.1016/B978-0-12-801238-3.98874-3.
  8. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018 May;14(5):270-284. doi: 10.1038/nrendo.2018.24. 
  9. Capozzi A, Scambia G, Pontecorvi A, Lello S. Hyperprolactinemia: pathophysiology and therapeutic approach. Gynecol Endocrinol. 2015 Jul;31(7):506-10. doi: 10.3109/09513590.2015.1017810. 
  10. Romijn JA. Hyperprolactinemia and prolactinoma. Handb Clin Neurol. 2014;124:185-95. doi: 10.1016/B978-0-444-59602-4.00013-7.