secondary amenorrhea

Amenorrhoea

Secondary

Amenorrhea

GENERAL OBJECTIVE

Students will understand secondary amenorrhoea and causes as well as management.

Specific objectives

After attending lecture, the student will can:
Know what is the secondary amenorrhoea.
List causes of secondary amenorrhoea.
Given patient history ,examination and a set of laboratory data, correctly diagnose the disease. (problem-solving).
Discuses treatment.


Secondary amenorrhea
is defined as the cessation of menses for ≥ 6 months in women of reproductive age and not due to pregnancy.
Practically speaking, a menstrual cycle interval of more than 90 days should be an indication for an evaluation to seek the cause.
Oligomenorrhea is defined as menses occurring at intervals longer than 35 days.

Causes:

A patient who has previously menstruated must have a patent lower genital tract, endometrium responding to ovarian hormones and ovaries which have responded to gonadotrophins.

Causes:

1. Uterus:
a. pregnancy.
In every case pregnancy must be excluded, even if the patient thinks it to be unlikely.
b. endometrium can be destroyed by the following:
Asherman's syndrome.
Endometrial tuberculosis.
Severe postpartum infection.
Endometrial ablation (therapeutic).

Causes:

2. Ovary:
Poly cystic ovary syndrome (PCOS).
Premature ovarian failure.
Resistant ovary syndrome.
Autoimmune ovarian failure.
Radiation and chemotherapy.
Functioning ovarian tumour (virilizing tumours).


Causes:
3. Thyroid disease :( hypothyroidism, hyperthyroidism).

Cranium:

Hypothalamus:
Weight change, anorexia nervosa, Starvation, obesity.
Stress.
Pseudocyesis
Trauma as severe head injury.

Pituitary :

Destruction by radiation.
Sheehan's syndrome
Hyperprolactinaemia

4. Drugs: (phenothiazine, metoclopromide, oral contraceptive pills after Stopped) cocaine and opioids.

5. general disease:

Any debilitating disease as pulmonary tuberculosis, Addison's disease, Chronic renal failure.

Management:

A thorough history and a careful examination should always be carried out before investigations are requested.


History: adequate history is essential.
Previous menstrual history
Age of menarche, concentrate on asking its nature spontaneous not primary amenorrhoea with withdrawal bleeding. A history of secondary amenorrhoea may be misleading, as the ‘periods’ may have been the result of exogenous hormone administration in a patient who was being treated with hormone replacement therapy (HRT) for primary amenorrhoea.
Ask about last menstrual bleeding ( LMP) and any symptoms of pregnancy as pregnancy is the most common cause of amenorrhea.

Past obstetric history:

History of curettage for secondary postpartum bleeding suggest diagnosis of Asherman's syndrome.
History of severe postpartum haemorrhage with history of failed lactation raise the possibility of Sheehan's syndrome.
History of severe postpartum infection.

Contraceptive history:

In some cases, the hormonal contraception itself may be the cause of the amenorrhea as:
Mirena (progestrone IUD), medroxy progesterone acetate, after stopping of combined oral contraceptive pills.

Presence of menopausal symptoms: History of hot flushes ( premature ovarian failure).

History of hairsutism, any change in hair growth and asked about acne (PCO, adrenal disturbance)
History in change in body weight as obesity or sudden loss of weight.
Elicit a history regarding the type of exercise activity and its duration per week. More than 8 hours of vigorous exercise a week may cause amenorrhea.

Presence of galactorrhea (milk produced in non lactatating breast). (The absence of this does not exclude hyperprolactinaemia)
Loss of menstrual regularity is an indication for a careful review of systems. The menstrual cycle should be viewed as a vital sign. Loss of menstrual regularity may be the first clear symptom allarming the onset of a major illness or systemic disease. Viewing the menstrual cycle as a vital sign may lead to earlier diagnosis of, and intervention for, several potentially life-threatening disorders.
History of headache, visual disturbance, Visual filed defect (pituitary tumour).


Past medical and surgical history as debilitating illness, endometrial ablation, previous curettage.
Drug history (reserpine, digoxin, phenothiazines and hormones, chemotherapy, radiation)
Family history of autoimmune disease, premature menopause (ovarian failure, fertility problems may also give clues to the aetiology.
Psychological history.

Physical examination:

Physical examination should begin with an overall assessment of body build and general health and hair distribution.
Looking particularly at stature and body form, secondary sexual development and the external genitalia.

Measure height and weight and body mass index (BMI). The normal range is 20–25 kg/m2, and a value above or below this range may suggest a diagnosis of weight related amenorrhoea.
Blood pressure measurement.
Signs of hyperandrogenism (acne, hirsutism, balding (alopecia)), and signs of virilization (deepening of the voice, breast atrophy, increase in muscle bulk and cliteromegaly).

Look for evidence for chronic disease as Uraemia, cachexia, vitiligo

thin skin, striae, and evidence of easy bruising.
If there is suspicion of a pituitary tumour, the patient’s visual fields should be checked.
Signs of endocrine disease.
Thyroid disease is common and the thyroid gland should be palpated and look for signs of hypothyroidism or hyperthyroidism.

Breast examination for:

State of breast development.
Any sign of pregnancy.
Milk secreation (galagtorrhoea).


Abdominal examination:
A general physical examination may uncover unexpected findings that are indirectly related to the loss of menstrual regularity (eg, discovery of hepatosplenomegaly, which may lead to detection of a chronic systemic disease).
Uterine enlargement in pregnancy.

Pelvic examination:

If the patient married, pelvic examination should be done.
Look for signs of pregnancy pregnancy.
Look for evidence of atrophic effects of hypo-oestrogenism within the lower genital tract. Thin and pale vaginal mucosa with absent rugae is evidence of estrogen deficiency.

Investigations:

In most cases, clinical variables alone are not adequate to define the pathophysiologic mechanism disrupting the menstrual cycle and needs investigations directed by history and examination.
All women who present with 3 months without cycle should have a diagnostic evaluation (history, examination, investigation).
The investigations are listed below, (putting in your mind that not all investigations should be done to all patients)

Investigations:

If there is suspicion of organic disease, it is mandatory to undertake the fullest investigation necessary to reach a precise diagnosis.

Investigations:Hormonal assay:

*Serum ß-hCG is recommended as a first step in evaluation of a secondary amenorrhea as Pregnancy is the most common cause of secondary amenorrhea.
*Prolactin level.
*Gonadotrophin level (FSH, LH)


Investigations:
Elevated Gonadotrophin level seen in premature ovarian failure and primary ovarian insufficiency. An FSH level in the menopausal range (>40IU) is indicative of ovarian insufficiency.
Reduced Gonadotrophin level seen in pituitary or hypothalamic disorder.

* Serum estradiol level.

*Thyroid function test.
*Androgen profile.

Karyotype:

Indicated in women less than 30 years of age who present with premature ovarian failure.

Autoimmune screen indicated in women with premature ovarian failure.

Imaging study:
Imaging ultrasound or CT/ MRI scanning for complicated cases of pelvic organ or intracranial lesion.

Hysterosalpingography and hysteroscopy are indicated in cases of possible Asherman's syndrome.

Laproscopy to inspect pelvic organs and to take biopsy of ovaries. if the biopsy revealed presence of primordial follicle mean resistant ovary syndrome while if there is no primordial follicle in ovarian biopsy mean premature ovarian failure.

Progesterone challenge test (Progesterone withdrawal test):

Prior to the development of readily available assays to measure serum levels of estradiol, the progesterone challenge test was used as a bioassay with which to demonstrate estrogen effect at the level of the endometrium but it can provide inappropriately reassuring information that may delay the etiology of ovarian insufficiency.


Treatment:
The treatment of a patient with amenorrhoea is specific to diagnosis.

Medical therapy:

*Anovulation:
In patient desire pregnancy, ovulation induction agents as clomiphene or gonadotrophins may be used.
In patient not desire pregnancy can use combined oral contraceptive pills or cyclic progestogens.

*Premature menopause is managed as menopause use hormone replacement therapy (HRT) to prevent osteoporosis.

*hyperprolactinemia

Use Dopamine agonists (Bromocriptine) 2.5mg daily for three days then 2.5 mg twice a day for six months. It should be stopped if pregnancy occurs. Cycle retain once Prolactin levels are retain normal.
Surgical treatment should be performed for patients with significant visual field defects or symptoms that can not be relieved by medical therapy.

*Pituitary insufficiency can be managed by replacing target organ hormones as well as HRT as for menopausal symptoms.

*If there is no evidence of underlying disease and thought that amenorrhea caused by stress or an emotional problem, we can act according to desire for pregnancy or contraception:
*If pregnancy is not desired, and no need for contraception, reassurance and spontaneous recovery is to be expected.
*If pregnancy is not desired and there is need for contraception, oral contraceptive is a good choice to restore menstrual cyclicity and provide estrogen replacement. The absence of pregnancy should be documented before oral contraceptive therapy is begun.
*If pregnancy is desired, ovulation induction is arranged.


*In anorexia nervosa restore weight to normal.
*In gross obesity, weight loss is advised.
*PCO treatment (in other lecture)

Surgical treatment

Some pituitary and hypothalamic tumors may require surgery and, in some cases, radiation.
Asherman's syndrome requires hysteroscopic lysis of the intrauterine adhesions.

Complications

Loss of menstrual regularity has been associated with an increased risk of wrist and hip fractures related to reduce bone density (osteoporosis).