What Causes Amenorrhea ?

Hypothalamic Causes Of amenorrhea.

•  Craniopharyngioma (a brain tumor near the pituitary gland).
•  Teratoma (a tumor made up of a mixture of tissues).
•  Sarcoidosis (a chronic disease of unknown cause characterized by the  formation of nodules in different parts of the body).
•  Kallmann syndrome (deficiency of gonadotropins, which promote growth and function of reproductive organs)
• Low body weight or growth delay.

Ovarian Causes:

•  Anovulation (lack of the release of an egg).
•  Hyperandrogenemia (high blood levels of male hormones).
•  Polycystic ovary syndrome (hormonal disorder affecting women of reproductive age).
•  Premature ovarian failure.
•  Turner syndrome (a genetic disorder characterized by underdeveloped ovaries, absence of menstrual onset, and short stature).
•  Pure gonadal dysgenesis (defective development of the ovary).
•  Autoimmune oophoritis (cells of the ovaries destroyed by the body’s own defense system).
•  Radiation or chemotherapy.
•  Anatomical abnormalities of the genital tract.
•  Intrauterine adhesions (the opposing surfaces of the uterine cavity stick together).
•  Imperforate hymen (a hymen in which there is no opening, the membrane completely closes off the vagina).
•  Transverse vaginal septum (a dividing wall or membrane in the vagina).
•  Aplasia (absence of an organ or tissue) of the vagina, the cervix, or the uterus.

Pathophysiology of Amenorrhea

Normally, the hypothalamus generates pulses of gonadotropin-releasing hormone
(GnRH). GnRH stimulates the pituitary to produce gonadotropins (follicle-stimulating hormone and luteinizing hormone), which are released into the bloodstream.
Gonadotropins stimulate the ovaries to produce estrogen (mainly estradiol), androgens (mainly testosterone), and progesterone. These hormones cause the following:

•  FSH stimulates tissues around the developing oocytes to convert testosterone to estradiol.
• Estrogen stimulates the endometrium, causing it to proliferate.
•  LH, when it surges during the menstrual cycle, promotes maturation of the dominant oocyte, release of the oocyte, and formation of the corpus luteum, which produces progesterone.
•  Progesterone changes the endometrium into a secretory structure and
  prepares it for egg implantation.

If pregnancy does not occur, estrogen and progesterone production decreases, and the endometrium breaks down and is sloughed during menses. Menstruation occurs 14 days after ovulation in typical cycles.

When part of this system malfunctions, ovulatory dysfunction occurs; the cycle of
gonadotropin stimulated estrogen production and cyclic endometrial changes
are disrupted, and menstrual flow does not occur, resulting in anovulatory amenorrhea. Most amenorrhea, particularly secondary amenorrhea, is anovulatory. However, amenorrhea can occur when ovulation is normal, as occurs when genital anatomic abnormalities (e.g. congenital anomalies causing outflow obstruction, intrauterine adhesions, etc.) prevent normal menstrual flow despite normal hormonal
stimulation.

Amenorrhea Signs and Symptom

Amenorrhea is a symptom of an underlying disorder rather than a condition
in and of itself. A female with primary amenorrhea will have no menstrual flow with or without other signs of puberty. In a female with secondary amenorrhea, additional symptoms may be present depending on the associated condition.

• Breast size changes.
• Voice changes.
•  Galactorrhea, headache, or reduced peripheral vision could be a sign of an intracranial tumor.
•  Increased hair growth in a male pattern (hirsutism) may be caused by excess androgen.
•  Vaginal dryness, hot flashes, night sweats, or disordered sleep may be a sign of ovarian insufficiency or premature ovarian failure.
•  Noticeable weight gain or weight loss may be present.
•  Excessive anxiety may be present in women with associated psychiatric abnormalities.

If amenorrhea is caused by a pituitary tumor, there may be other symptoms related to the tumor, such as vision loss and headache.

Diagnosis Of Primary And Secondary Amenorrhea

1. Diagnosing Primary Amenorrhea: Primary amenorrhea can be diagnosed in women by age 14 if no secondary sex characteristics, such as enlarged breasts and body hair, are present. In the absence of secondary sex characteristics, the most common cause of amenorrhoea is low levels of FSH and LH caused by a delay in puberty. If secondary sex characteristics are present, but menstruation is not, primary amenorrhea can be diagnosed by age 16. A reason for this occurrence may be that a person phenotypically female but genetically male, a situation known as androgen insensitivity syndrome. Mullerian agenesis (is a congenital malformation characterized by a failure of the Mullerian duct to develop, resulting in a missing uterus and variable degrees of vaginal hypoplasia of its upper portion. It is the most common cause of primary amenorrhea) causes around 15% of primary amenorrhea cases. If a uterus is present, outflow track obstruction may be responsible for primary amenorrhea.

2. Diagnosing Secondary Amenorrhea: The diagnosis of amenorrhea requires a careful medical history to document the presence of amenorrhea as well as any other coexisting medical conditions that may be the cause of amenorrhea. A physical examination, including a pelvic examination is also performed.

Depending upon the results of the history and physical examination further
diagnostic tests may be ordered. Blood tests may be ordered to examine the levels of
ovarian, pituitary and thyroid hormones. These tests may include measurements of
prolactin, follicle-stimulating hormone (FSH), estrogen, thyrotropin, dehydroepiandro sterone sulfate (DHEA-S), and testosterone. For some individuals, a pregnancy test is the first test perfomed. Imaging studies, such as ultrasound, X-ray, and CT or MRI scanning may also be recommended in certain individuals to help establish the cause of amenorrhea.

Treatment For Primary and Secondary Amenorrhea

Treatment of primary and secondary amenorrhea is determined by the precise
cause. Treatment goals can be to relieve symptoms of hormonal imbalance, establish
menstruation, prevent complications, and to achieve fertility.

Medical Treatment: Some causes of amenorrhea can be managed by drug
therapy.

Dopamine agonists: In most women, treatment with dopamine agonists medications restores normal ovarian endocrine function and ovulation. e.g. Bromocriptine, or Pergolide are effective in treating hyperprolactinemia. Hormone replacement therapy: An
estrogen and a progestin can be used for women in whom estrogen deficiency remains because ovarian function cannot be restored.

Metformin: May used in women with polycystic ovary syndrome to induce ovulation. In premature ovarian failure, hormone therapy may be recommended both to avoid the unpleasant symptoms of estrogen depletion as well as prevent complications of low estrogen level such as osteoporosis.

Amenorrhea Surgery: Amenorrhea caused by pituitary and hypothalamic tumors or structural blockage may require surgery and, in some cases, radiation
therapy.

Hirsutism

Hirsutism is the growth of excessive hair in a male pattern which include face, chest, abdomen and back and usually due to the increased production of androgens (male
hormones). Disorders in which hirsutism are seen, include: polycystic ovarian syndrome, congenital adrenal hyperplasia, ovarian tumors or adrenal tumors. Blood tests are
used to help determine a cause. Occasionally, there is no cause found for the hair growth (idiopathic hirsutism). Medical treatment varies by the underlying cause of the hirsutism. Topical treatments including electrolysis and laser can be used to decrease hair growth.

Androgen Excess

Androgen excess refers to the overproduction of male hormones. This can result from ovarian or adrenal tumors. Other disorders such as polycystic ovarian syndrome, Cushing’s syndrome (the overproduction of cortisol), hyperprolactinemia and congenital adrenal
hyperplasia can cause extra male hormones to be produced. In women androgen excess
can cause hirsutism (excessive hair growth), acne, male pattern baldness, menstrual cycle
irregularities and infertility. Diagnosis is generally made through blood tests. CT scans of adrenal glands and ovaries are occasionally needed. Treatments vary by the underlying cause of the androgen excess.

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