ABSENT AND IRREGULAR MENSES: CAUSES AND DIFFERENTIALS

CONTENT

-INTRODUCTION

-CAUSES

-DIFFERENTIAL DIAGNOSES

 

INTRODUCTION

Commonly, disorders of the menstrual cycle may present as absent and irregular menses. These are both medically referred to as amenorrhea and oligomenorrhea respectively. Because a normal menstrual cycle, has a cycle length of about 21 to 35 days, any menstrual cycle, whose length is longer than 35 days is regarded as abnormal and is often associated with anovulatory and irregular cycles. For more information on what constitute a normal menstrual cycle please read NORMAL AND ABNORMAL MENSTRUAL CYCLES. Oligomenorrhea can be defined as the presence of irregular menses associated with a delay in menstrual flow of more than 35 days but less than 6 months while amenorrhea simply means absence or cessation of menses. Although oligomenorrhea is usually as a result of disorders affecting or preventing ovulation, amenorrhea may either be due to disorders of ovulation or to an obstruction of the outflow of the menstrual period along the female genital tract. It can furthermore be divided into primary and secondary amenorrhea depending on clinical presentation.

PRIMARY AMENORRHEA

This refers to a delay in the onset of menses by the age of 16 in a young girl, or the absence of menstruation in a young girl after two years of development of secondary sexual characteristics or the absence of secondary sexual characterisitcs in a young girl by the age of 14, whichever comes first. Because primary amenorrhea occur in the context of delayed and abnormal puberty, it’s causes, presentation, investigation and management will be discussed in the section on this site dedicated to delayed and abnormal puberty.

SECONDARY AMENORRHEA

This refers to the absence of menstrual flow for a period of six months or more in a woman who had previously been menstruating regularly, after excluding, pregnancy, lactation (breast feeding) and menopause. Causes are varied and include any disorder that affect the HPO axis (resulting in anovulation) or any obstruction to the outflow of the menstrual period along the female genital tract secondary to damage to the internal lining of the uterus, cervix or the vagina. 

OLIGOMENORRHEA

This as mentioned above, refers to any menstrual cycle whose length is longer than 35 days but shorter than six months. Usually associated with irregular and infrequent menses, its causes include diseases, factors and disorders that disrupt the HPO axis, sharing many of the causes of secondary amenorrhea except those that obstruct the outflow of menses along the female genital tract.

 

CAUSES

DISORDERS OF THE HPO AXIS

The HPO axis is the term used to describe the seamless interactions of the hypothalamus, pituitary gland and the ovary that result in the creation of a regular ovulatory or a normal menstrual cycle. For more on how these three work together to control the events of the menstrual cycle please read MENSTRUAL CYCLE, OVULATION AND MENSTRUATION: EXPLANATION OF BASIC PHYSIOLOGY or CHAT WITH OUR CONSULTANTS. Therefore, any disease or factors affecting any part of the HPO axis can disrupt the axis, thereby preventing ovulation and the resulting in irregular or absent menses. These disorders can be classified based on the site of disruption of the HPO axis into:

1.  DISORDERS OF THE HYPOTHALAMUS

The hypothalamus secrete the hormone GnRH, which in turn controls and stimulates the pituitary gland to produce hormones responsible for controlling the activities of the ovaries including ovulation. Disorders, lesions, diseases and factors that prevent or disrupt the release of this hormone, will prevent the proper stimulation of the pituitary gland by the hypothalmus. Similalrly, Dopamine, another hormone released by the hypothalamus, is responsible for keeping in check the excessive production of the hormone Prolactin by the pituitary gland. Prolactin is the hormone responsible for the production of breast milk in both pregnant and breast feeding women. In non pregnant women, abnormally high levels of prolactin can disrupt ovarian activities resulting in irregular ovulation and infertility as well as the discharge of breast milk from the nipples, a term referred to as galactorrhea. Hence, any factors, diseases, lesions or tumours that prevent the release of either or both of GnRH and Dopamine by the hypothalamus can hinder ovulation and result in irregular and absent menses. These include:

1)  FACTORS THAT MAY SWITCH OFF THE RELEASE OF GnRH FROM THE HYPOTHALAMUS

1.  Excessive exercise

2.  Weight loss from chronic illness, starvation and more commonly from anorexia nervosa in young girls.

3.  Stress including that from chronic illnesses and psychological disturbances.

2)  TUMOURS THAT CAN COMPRESS THE HYPOTHALAMUS

These tumors disrupt the HPO axis by preventing the secretion of dopamine by the hypothalamus thus allowing high proactin secretion which inturn disrupt the HPO axis. They include:

1.  Craniopharyngioma

2.  Glioma

3)  DRUGS THAT CAN BLOCK THE SECRETION OF GnRH OR OPPOSE THE ACTIVITY OF DOPAMINE

1.  Progestogens

2.  Hormone replacement therapy (HRT)

3.  Dopamine antagonists

4)  OTHERS

These are generally rare:

1.  Sarcoidosis; by infiltrating the hypothalamus

2.  Tuberculosis; by infiltrating the hypothalamus

3.  Head injuries

2.  DISORDERS OF THE PITUITARY GLAND

The pituitary gland seretes two hormones FSH and LH that systematically control the activities of the ovaries. Disruption of the secretion of these two hormones will result in disruption of the HPO axis. The following are disorders of the pituitary gland that may disrupt the HPO axis:

1)  Pituitary adenomas; these are benign but abnormal group of hormone secreting cells who either by the hormones they secrete or the pressure effect of their mass on surrounding tissues, may disrupt the normal secretion of the pituitary glands incuding that of FSH and LH. The commonest are Prolactinomas, a tumor that releases high levels of prolactin hormone which inturn disrupt the ovarian activiites.

2)  Pituitary infarction or necrosis; the death of the pituitary cells such as that following Sheehan’s syndrome may shut down the secretion of hormones produced by the pituitary gland leading to wide spread hormonal deficiencies including absent menses.

3)  Thyroid disorders: Although hypothyroidism may directly cause heavy menstrual flow, primary hypothyroidism may result in irregular menstruation. This is due to the increased level of thyrotropin releasing hormone (TRH) produced by the hypothalamus in response to reduced levels of thyroid hormones in the blood which in turn stimulates the pituitary gland to secrete high levels of the prolactin hormone. The high proloctin level thereafter, results in a disruption of the HPO axis preventing ovulation and causing absent and irregular menses. Hyperthyroidism on the other burns out the body so much that the excess weight loss and stress from the increased metabolic rate result in amenorrhea and scanty menses.

3.  DISORDERS OF THE OVARY

SInce the ovary is the seat of ovulation, any disorder of the ovary that impair ovulation will result in irregular and absent menses. These include:

1)  Polycystic ovarian syndrome

2) Premature ovarian failure (POF). POF, defined as cessation of menstrual periods before the age of 40, is usually unexplained. Secondary causes may however include, chemotherapy, radiotherapy, autoimmune disease and chromosomal disorders (e.g. Turner’s 45XO/46XX).

 

DIFFERENTIAL DIAGNOSES

These are conditions, disorders and diseases that may present similarly to but are not due to disorders of the HPO axis.

1.  They include structural disorders that result following injury or trauma to the inner lining of the uterus and any other part of the female outflow tract resulting in the formation of scar tissues that subsequently obstruct the passage or flow of the menstruum during menstruation. The causes, investigation and management of these disorders have been discussed in the section dedicated to reduced mentrual flow. They incude:

1)  Asherman syndrome/uterine synechiae

2)  Cervical stenosis

3)  Acquired vaginal gynaetresia.

For more information, read REDUCED MENSTRUAL FLOW: INTRODUCTION AND CAUSES or CHAT WITH OUR CONSULTANTS.

2.  pregnancy

3.  Immaturity of the HPO axis 

 

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