2

Chapter 2: Menstrual disturbance

Primary amenorrhea: is the absence of menstruation by the age of 14 when 2ry sexual characters are
absent or by the age of 16, in the presence of 2ry sexual characters.
Secondary amenorrhea: is cessation of menstruation for a length of time equivalent to 3 previous
cycle intervals or 6 months.
Delayed menarche: means spontaneous onset of menstruation in a woman older than 16 years in
absence of reproductive abnormalities.

I. Physiological amenorrhea

Before puberty: due to the low secretion of GnRH.

After menopause: due to depletion of ovarian follicles; thus lack of response to gonadotrophins.
During pregnancy: due to continuous estrogen and progesterone production without withdrawal.
During lactation: prolactin suppresses GnRH, renders the ovary refractory to the action of

gonadotrophins, and inhibits ovarian steroidogenesis.

Perimenarche: due to HPO axis immaturity.
Perimenopause: due to decreased ovarian follicles and increased resistance to gonadotrophins.
II. Pathological amenorrhea

A. Primary Amenorrhea
The most common causes are gonadal dysgenesis (43%), and Mllarian duct anomalies (15%).

Group A: Patients with well developed secondary sexual characters

Uterus present
Uterus absent
Compartment I
Compartment II
Compartment I
Compartment II
(Outflow factor)
(Ovarian factor)
(Outflow factor)
(Ovarian factor)
Cryptomenorrhea
Polycystic ovary
Mllerian agenesis
Androgen insensitivity
syndrome.
syndrome
Group B: Patients with poorly developed secondary sexual characters
Compartment II
Compartment III
Compartment IV
(Ovarian factor)
(Pituitary factor)
(Hypothalamic factor)
Gonadal dysgenesis
Lorian syndrome
Kallman syndrome
Resistant ovary syndrome
Empty sella syndrome
Frolish syndrome
Gigantism (acidophil adenoma) Laurance-Moon-Biedl syndrome
Group C: Patients with heterosexual characters
Ovarian causes
Adrenal causes
Virilizing tumors
Congenital adrenal hyperplasia
Androgen secreting tumors

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Chapter 2: Menstrual disturbance

B. Secondary Amenorrhea
The most common cause of secondary amenorrhea is pregnancy then chronic Anovulation, hypothyroidism, and
hyperpolactinemia.

Compartment IV (Hypothalamic factor)

Functional causes
Organic causes
Anorexia nervosa
Tumors (craniopharyngioma)
Pseudocyesis
Inflammation (meningitis, encephalitis)
Severe exercise (Jogger's amenorrhea)
Trauma (fracture skull)
Mental disease/emotional stress
Postpill amenorrhea (Shearman
syndrome)
Compartment III (Pituitary factor)

Functional causes
Drugs causing hyperprolactinemia e.g.
tranquilizers, reserpine,
phenothiazines.

Organic causes

Trauma.
Infection.
Tumors either secreting prolactin
"prolactinoma", ACTH causing Cushing
syndrome or GH causing acromegaly.
Pituitary cachexia: Sheehan Syndrome and
Simmonds disease.
Compartment II (Ovarian factor)
Functional causes
Organic causes
Polycystic ovary syndrome.
Surgical removal (bilateral oophorectomy).
Premature ovarian failure.
Destruction by radiotherapy, chemotherapy.
Androgen secreting tumors.
Compartment I (Uterine and outflow factor)
TB or post-irradiation or gangrenous endometritis.
Asherman syndrome.
Hysterectomy.
Acquired cryptomenorrhea due to cervical stenosis following amputation or cauterization.
General causes
Severe anemia, malnutrition, and obesity.
DM, Pulmonary TB, and chronic nephritis.
Thyroid disease (autoimmune thryroiditis & hypothyroidism).
Adrenal diseases (androgen secreting tumors, Addison disease).
Bronchogenic carcinoma (ACTH producing).

A point to explain:

Compartment I: Disorders of the outflow tract or uterine target organ.

Compartment II: Disorders of the ovary.

Compartment III: Disorders of the anterior pituitary.

Compartment IV: Disorders of central nervous system (hypothalamic) factors.

28 | P a g e

Chapter 2: Menstrual disturbance

I. History

History taking should cover the following topics carefully:

Pubertal history: did the patient have normal onset and progression of puberty?
Menstrual history: history of previous regular menstrual cycles and their characters.
History of present illness: the following points can help in diagnosis:
Complaint

Possibility

New-onset headaches or visual changes

Tumor of the CNS or pituitary gland

Spontaneous bilateral breast discharge

Hyperprolactinemia

Heat or cold intolerance, weight changes

Thyroid disease

Hot flashes and vaginal dryness

Premature ovarian failure (POF).

Hirsutism and acne

PCOS, or wit h late-onset CA H.

Cyclic pelvic pain

Tract outlet obstruction

Exercise, weight loss, chronic illness, illicit drug use

Hypothalamic amenorrhea

Anosmia

Kallmann syndrome

Sexual activity

Pregnancy

Contraceptive history:
COC users: postpill amenorrhea (3-6 months after pill stoppage) may occur in < 1% of users.
POC users: Amenorrhea associated with Injectables increases with time and persists after
stoppage for up to 9 months.
Medical history:
History of pelvic infection, radiation, chemotherapy, or other illness.
Any medications, especially those that increase prolactin levels such as antipsychotics.
Surgical history: prior intrauterine surgery e.g. D&C, and postoperative complications particularly
infection.
Family history: Important questions regarding family history include:
Hi story

Significance

Premature cessation of menses or a history of autoimmune disease.

Increased risk for POF

Family history of irregular menses, infertility, or hyperandrogenism

PCOS

Sudden neonatal death in family members

CYP21 gene mutation of CAH

Social history: exposure to environmental toxins, including cigarettes.

II. Examination

General examination: a thorough physical examination should include:

General appearance:
The following physical signs may give a clue for the diagnosis:

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Chapter 2: Menstrual disturbance

Physical finding

Significance

Low BMI, with loss of tooth enamel (recurrent vomiting)

Eating disorder

Midline facial defects e.g. cleft palate

Associated defect of the anterior pit uitary

Dysmorphic features (e.g., webbed neck, short stature)

Turners syndrome

Voice deepening and male pattern balding.

Virilization

Acanthosis nigricans, hirsutism, or acne

PCOS

Supraclavicular fat, abdominal striae with hypertension

Cushing syndrome

Enlarged thyroid, delayed reflexes, and bradycardia

Hypothyroidism

Bilateral galactorrhea

Hyperprolactinemia

Assessment of secondary sexual character development (Tanner staging):

Staging

Breast development

Pubic hair development

Tanner 1

Prepubertal

Prepubertal

Tanner 2

Breast bud stage, elevation of breast and

Sparse long, slightly pigmented hair, along

papilla; enlargement of areola

labia

Further enlargement of breast and areola.

Dark, coarse and curled hair, spreading

Tanner 3

sparsely over mons pubis

Tanner 4
Tanner 5

Areola and papilla form a secondary

Hair adult in type, but no spread to medial

mound above level of breast

surface of thighs

Mature stage, recession of areola to

Adult in type and quantity, with horizont al

breast contour

distribution ("feminine")

According to this, the following is the normal squeal for pubertal growth:
Breast development

Pubic hair development

Stage of development

Age in years

Initial growth acceleration

8-10

Thelarche

9-11

Adrenarc he

9-11

Peak growth

11-13

Menarche

12-14

Adult characteristics

14-16

Local examination:
Examination of the genitalia includes:
Sparse or absent female pubic hair: Lack of adrenarc he or androgen insensitivity syndrome
Male pattern of genital hair growth, noticeably clitoromegaly: Virilization
A pink moist vagina and cervical mucus: Evidence of estrogen production
Uterus above an obstruction at the level of the introitus or in the vagina by rectal examination:
suggesting hematocolpos
III. Investigations

The following algorithms show how to investigate a case of amenorrhea: primary/secondary

30 | P a g e

Chapter 2: Menstrual disturbance

Investigations for a case of primary amenorrhea
Assessment of secondary sexual characters

Pelvic Ultrasonography

Serum FSH & LH

Low FSH & LH (< 5
IU/L)

High FSH & LH (> 20,

> 40 IU/L)

Hypogonadotrophic
hypogonadism

Hypergonadotrophic
hypogonadism

Uterus absent

Uterus present

Karyotyping

Outflow obstruction

46 XY

Yes

45 XO

Karyotyping

CT and MRI for

hypothalamic and
pituitary evaluation

46 XX

45 XO

Premature
ovarian
failure

Turner
syndrome

Cryptomeorrhea

Mullarian Androgen
agenesis insensitivity
syndrome

No
Follow the
steps of
secondary
amenorrhea

Investigations for a case of secondary amenorrhea

Exclusion of pregnancy is the 1st step, if negative, check TSH &
prolactin

Both are normal

Abnormal TSH

Progestogen
challenge test

Thyroid
disease

Withdrawal bleeding

No withdrawal bleeding

Withdrawal bleeding
FSH & LH
assessment
Low FSH & LH (< 5 IU/L)
Hypogonadotrophic hypogonadism

31 | P a g e

Prolactin
< 100 ng/mL

Prolactin
> 100 ng/mL

Consider
other causes

MRI to evaluate for

prolactinoma

Estrogen/progestogen
challenge test

Anovulation

CT and MRI for

hypothalamic and
pituitary evaluation

Normal TSH, high prolactin

No withdrawal bleeding
Uterine /Outflow
cause

High FSH & LH (> 20, > 40 IU/L)

Hypergonadotrophic
hypogonadism

Negative
Consider
other causes

Chapter 2: Menstrual disturbance

Laboratory Testing:
Exclusion of Pregnancy: (urinary or serum -hCG level) for all sexually active women.
Hormonal withdrawal tests:
Progesterone withdrawal test

Estrogen and Progesterone

withdrawal test

Test

10 mg of MPA is given daily for 5

CoCs are given for 21 days then

successive days, bleeding is expected

stopped, This should be followed by

within 7-10 days.

bleeding

Posi tive test

Anovulation

Intact uterus & patent out flow

Negative test

Estrogen progesterone withdrawal is

If again fails to bleed, anatomical

indicated

abnormality is diagnosed

Drawbacks

False positive results due to

fluctuating estrogen levels in early
stages ovarian failure that causes
some bleeding.

False negative results in women with

high androgen (PCOS and CAH),
due to atrophic endometrium

GnRH stimulation test:

Indication: to differentiate hypothalamic from pituitary causes if gonadotrophin value is low.
Test: IV bolus injection of 100 g of GnRH followed by measurement of LH and FSH at 0, 15,
30, 45, and 60 minutes.
Result:
In hypothalamic disease: 3-10 fold increase in LH, 1.5-3 fold increase in FSH within 15-30
minutes (normal response).
In pituitary disease: absent response.
Serum Hormone Levels:
Indications: Any woman found to have a normal pelvic examination.
Tests:
Primary laboratory te sts
Follicle-Stimulating Hormone (FSH):
Elevated level: (2 FS H levels > 40 mIU/mL at

least 1 month apart ) in ovarian failure.

Low level: hypothalamic-pit uitary dysfunction.
LH:FSH level ratios: > 2 in PCO patients

(60% of cases).
Prolactin and TSH: for thyroid dys function and
hyperprolactinemia.

Secondary laboratory tests

Serum testosterone (N= 20 to 80 ng/dL):
200 ng per dL: Hy perandrogenic chronic

Anovulation.
> 200 ng per dL: androgen-secreting tumor.

Serum DHEAS (N= 250-300 ng/dL):

700 ng per dL: Hy perandrogenic chronic

Anovulation
> 700 ng per dL: adrenal or ovarian tumor.

Serum 17-OH progesterone (N= < 200 ng/dL:

> 400 ng/dL: Consider adrenoc orticotropic

stimulation test to diagnose CA H

Imaging Tests:
Sonography: for diagnosis of PCO, determination of the presence of the uterus.

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Chapter 2: Menstrual disturbance

CT & MRI:
Indications: done for any patient with hypogonadotropic hypogonadism. Functional
hypothalamic amenorrhea is a diagnosis of exclusion.
Results: destructive disorders or infiltrative diseases of the hypothalamus or pituitary.
Chromosomal Analysis: indicated in:
Patients with gonadal dysgenesis (up to age 35 years) to identify Y chromosome requiring bilateral
oophorectomy.
Patients with absent uterus for differentiation between AIS and Mullarian agenesis.
Patient with a familial history of POF.

General treatment

Proper diet, correction of weight, treatment of anaemia,

chronic illness, psychotherapy if necessary.
Treatment of the cause

Anatomic abnormalities: surgical correction, if possible.

Hypothyroidism: thyroid replacement.
Hyperprolactinemia: treatment of cause, dopamine agonists
Late-onset CA H: low-dose corticosteroids to partially block ACTH stimulation
Management according to patient complaint

Absence of menstruation only

Infertility

Hormonal treatment is given if no response has

Fertility usually regains after treatment of the caus e.

occurred following treatment of the cause or if no

However, POF is only treated with egg donation

cause has been identified (functional)

which is prohibited in our count ries.

COCs are given cyclically for 3 successive cycles to

Induction of ovulation is given according to WHO

restore normal rhythm

classification of causes of anovulation

WHO Class I

WHO Class II

WHO Class III

Hyperprolactinemic

(Hypogonadotrphic

(Normogonadotrphic

(Hypergonadotrphic

anovulation

hypogonadal)

normoestrogenic)

hypoestrogenic)

Hypothalamic/Pituitary

e.g. PCOS

POF

Pulsatile GnRH or

Clomiphene citrate or

Egg donation

goadotrophins

gonadotrophins

(prohibited)

33 | P a g e

Dopamine agonists

Chapter 2: Menstrual disturbance

NIH definition (1990)

To include both of the following:
Oligo-ovulation.
Hyperandrogenism and/or hyperandrogenemia (with the exclusion of related dis orders)
ESHRE/AS RM (Rotterdam conference) definition (2003)
To include two out of three of the following:
Oligo or anovulation
Clinical and/or biochemical signs of hy perandrogenism
Polycystic ovaries (with the exclusion of related disorders)
ASRM = American Society of Reproductive M edicine; ESHRE = European Society of Human Reproduction and Embryology; NIH =
National Institutes of Health.

PCOS is the most common cause of chronic anovulation (4 to 12 %).

The underlying cause is unknown. It is suggested to be multifactorial and polygenic. Alterations in GnRH
pulsatility lead to preferential production of LH compared with FSH.
Hypothalamus

Alternation of GnRH release

Abnormal

Pituitary gland

feedback

LH:FS H ratio
Adrenal

gland

Ovary (theca cells)

Androgen production

Abnormal lipid profile

Converted in adipose tissue

Estrone
Uterus

Skin

Insulin

Follicular

resistance

atresia

Acne, Hirsutism, acanthosis

negricans

Endometrial
hyperplasia

Anovulation/
amenorrhea

A point to explain: Insulin resistance is defined as a reduced glucose response t o a given amount of insulin. It is
due to a post binding abnormality in insulin receptor-mediated signal transduction.

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Chapter 2: Menstrual disturbance

Short-term consequence s

Long-term consequences

Menstrual disturbance

Diabetes mellitus

Hyperandrogenism

Cardiovascular disease

Infertility

Endometrial cancer

Obesity

Metabolic disturbances

Abnormal lipid profile/glucose intolerance

Clinical picture:
I. Classic presentation

Menstrual disturbance:
Type of menstrual disturbance:
The most common are amenorrhea or oligomenorrhea.
Patients may develop regular cycles later in life due to the decreasing ovarian follicles with
subsequent decrease in androgen production.
Cause of menstrual disturbance:
Chronic anovulation.
Atrophy of the endometrium due to exposure to androgens.
Differential diagnosis:
50% of postmenarchal girls have irregular periods for up to 2 years due to immaturity of the
HPO axis. In girls with PCOS, they often continue to have irregular cycles.
Hyperandrogenism:
Hirsutism:
Definition: The presence of coarse, dark, terminal hairs distributed in a male pattern.
Differential diagnosis: Hirsutism should be distinguished from hypertrichosis, which is a
generalized increase in lanugo, that is, the soft, lightly pigmented hair.
Acne: Acne that is persistent or of late onset should suggest PCOS.
Alopecia: androgenic alopecia is a less common finding in PCOS.
Acanthosis Nigricans:
Definition: thickened, gray-brown velvety plaques seen in areas of flexure such as the back of
the neck and the axillae.
Incidence: obese women with PCOS (50% incidence), PCOS and normal weight (5-10%).
Aetiology: Insulin resistance leads to hyperinsulinemia, which stimulates keratinocytes.
Obesity: The waist:hip ratio reflects an android or central pattern of obesity.
Infertility: PCOS is the most common cause of Anovulation and accounts for 80 to 90 % of cases.
Pregnancy Loss: early miscarriage may occur due to insulin resistance.
Complications in Pregnancy: higher risk of gestational diabetes, hypertension, preterm birth, and
perinatal mortality.
II. Atypical presentation

Ovarian Hyperthecosis: (rare)

It is a more severe form of PCOS, characterized by:

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Chapter 2: Menstrual disturbance

Nests of luteinized theca cells throughout the ovarian stroma.
Severe hyperandrogenism, and occasionally frank virilization.
A greater degree of insulin resistance and acanthosis nigricans.
HAIRAN Syndrome:
It consists of HyperAndrogenism-Insulin Resistance-Acanthosis Nigricans, uncommon.
Investigations:
I. Hormonal profile

Test

Significance

FSH & LH

LH is increas ed in 50% of affected women .

FSH is normal or decreased.

LH:FS H ratio (Day 3)

LH:FSH ratios > 2 in 60% of patients

Serum testosterone

Increased in 70-80% of patients.

Serum androstenedione

Increased

Serum DHEAS

Increased in 50% of cases

TSH and Prolactin

Exclusion of thyroid disease and hy perprolactinemia

(Prolactin is slightly increased in 25% )

17-Hydroxyproge sterone

Exclusion of congenital adrenal hyperplasia (CA H)

II. Assessment of insulin resistance

2-hour glucose tolerance test (2-hr GTT).

Fasting serum insulin level
Serum glucose:insulin ratios.
III. Lipid profile

Fasting lipid profile is essential in patients with PCO.

IV. Sonography

Sonographic criteria for polycystic ovarie s from the 2003 Rotterdam conference
The presence of 12 small cysts (2 to 9 mm in diameter) or
An increased ovarian volume (>10 mL) or
Often there is an increased amount of stroma relative to the number of follicles.

The typical "black pearl necklace" appearance is no more a diagnostic criterion because it can
often be found in other conditions of androgen excess, such as CAH, Cushing syndrome.
A polycystic ovary should not be confused with a multicystic ovary which is normal sized, contains
six or more follicles without peripheral displacement, or increase in central stromal volume.
V. Laparoscopy

Direct visualization of the ovaries and possible ovarian drilling could be done.
VI. Endometrial biopsy

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Chapter 2: Menstrual disturbance

It is recommended in women older than age 35 with abnormal bleeding and in younger women with
anovulatory bleeding refractory to hormonal treatment for fear of endometrial hyperplasia.

Other causes of oligo- or anovulation

Hyperthyroidism
Hypothyroidism
Hyperprolactinemia
Hypogonadotropic hypogonadism

Other causes of hyperandrogenism

Late-onset CAH
Cushing syndrome
Androgen-secreting ovarian tumor
Androgen-secreting adrenal tumor

I. General treatment

Life style changes (through a well-balanced hypocaloric diet and exercise) are very beneficial. Even 5%
reduction of body weight can result in restoration of normal ovulatory cycles in some women.
II. Treatment according to patient complaint

First: Patient complaining of menstrual disturbance

Combination Oral Contraceptive Pills:
Indication: A first-line treatment for menstrual irregularities.
Advantages:
It will induce regular menstrual cycles.
COCs reduce androgen levels (COCs suppress gonadotropin).
Estrogen component increases SHBG levels.
Progestin component antagonizes the endometrial proliferative effect of estrogen, thus
reducing risks of endometrial hyperplasia due to unopposed estrogen.
Cyclic Progestins:
Indication: In patients who are not candidates for combination hormonal contraception.
Regimen: MPA (medroxyprogesterone acetate), 5 to 10 mg orally daily day for 12 days.
Second: Patients complaining of hirsutism
Treatments may require 6 to 12 months before clinical improvement is apparent.
COCs

As described earlier.

GnRH Agonists

Administration of these agents is not a preferred long -term treatment method due
to associated bone loss, high cost, and menopausal side effects.

Antimetabolite creams
(Eflornithine)
Androgen-Receptor
Antagonists

It is applied twice daily to areas of facial hirsutism. Clinical results from eflornithine
hydrochloride may require 4 to 8 weeks of use.
These agents carry a risk for: pseudohermaphroditism in male fetuses in early
pregnancy. So, these drugs are used in conjunction with oral contraceptive pills.

5 -Reductase Inhibitors

Finasteride 5-mg daily dose is modestly effective in the treatment of hirs utism.

Hair Removal

Hirsutism is treated by mechanical means (depilation and epilation techniques).

Third: Women complaining of acne

Combination oral contraceptive pills.

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Chapter 2: Menstrual disturbance

Antiandrogens such as spironolactone, which inhibit binding of androgen to its receptor.
5 -reductase inhibitors e.g. finasteride.
Fourth: Patients complaining of infertility
Induction of ovulation:
Clomiphene citrate alone, with HCG or gonadotrophins with HCG.
Insulin-Sensitizing Agents: e.g. Metformin 250-500 mg 3 times daily. It improves peripheral insulin
sensitivity by reducing hepatic glucose production and increasing target tissue sensitivity to insulin.
Surgical treatment:
Laparoscopic ovarian drilling during which 4-8 points (depending on ovarian size) are cauterized in
each ovary with 60-400 watts for 2-4 seconds.
The rate of ovulation thereafter is 90%, the rate of pregnancy is 70%.
Assisted reproductive techniques: restored to if all other measures fail to achieve pregnancy.

Gonadal dysgenesis with abnormal Karyotype

(Turner syndrome)
An inherited disorder in which oocytes undergo accelerated atresia during early fetal ovary, and the
ovary is replaced by a fibrous streak due to abnormal karyotype (missed X chromosome).
about two thirds of gonadal dysgenesis.

45,XO karyotype: (50%) absent X chromosome (monosomy).

Chromosomal mosaicism: (50%)
The most common form is 45 XO/46 XX karyotype.
Chromosomal mosaicism may include the presence of a Y chromosome, such as 45 X/46,XY.
Thus, chromosomal analysis should be performed and a streak gonad should be removed if Y
chromosomal material is found, as 25% will develop a malignant germ cell tumor.
46 XX karyotype: with partial deletion of X chromosome (abnormal X chromosome).

I. Clinical presentation

I. Classic presentation (45 XO karyotype monosomy)

Symptoms:
Primary amenorrhea and delayed puberty.
Primary infertility.
Signs:
Short stature with webbing of the neck & shielding of the chest.
Cardiac (Coarctation) and renal anomalies.
Bilateral cubitus valgus (wide carrying angle).

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Chapter 2: Menstrual disturbance

Deformities of the ears, fingers and toes.

The breasts remain underdeveloped with widely spaced nipples.
The genital organs are infantile.
II. Presentation in patients with mosaic turner syndrome
When compared with the classic 45 XO patients, individuals with mosaic turner are:
Taller although 80% are shorter than their peers
Fewer abnormalities, 66% have some somatic abnormalities.
Spontaneous menstruation occurs in 20% of these patients ending in POF.
III. Presentation in patients with abnormal X chromosome
Patients with deletions on long arm of X chromosome (Xq): patients will have sexual infantilism,
normal stature, no somatic abnormalities, and streak gonads. Some patients may be eunuchoid in
appearance and have delayed epiphyseal closure.
Patients with deletions on short arm of X chromosome (Xp): phenotypically similar to individuals
with Turner syndrome.
II. Investigations

Hormonal profile: estrogen is law, FSH is high (hypoestrogenic hypergonadotrophic).

Buccal smear: absent Barr body.
Chromosomal study: 45 XO or mosaic.
Ultrasound & laparoscopy: infantile organs and streak gonads.
Investigations for other anomalies: e.g. chest X-ray.

General measures: the patient should be assessed for hypertension, DM and thyroid disorders.
Genetic counseling for other family members should be considered.
Hormonal treatment:
Growth hormone therapy: To achieve adequate final adult height.
Estrogen therapy:
Rule: To promote sexual maturation, induce menstruation and avoid osteoporosis.
Starting therapy: It starts at 12-13 years old when growth hormone therapy is completed, to
avoid premature closure of bone epiphyses.
Regimen: Conjugate Equine Estrogen (CEE) 0.3 - 0.625 mg is given daily and is increased
over 1-2 years till twice the dose of postmenopausal women (1.25 mg).
Progestins:
Rule: it is given to avoid the unopposed estrogen.
Starting therapy: it starts after the patient experiences vaginal bleeding or after 6 months of
unopposed estrogen if no bleeding occurs.
Regimen: MPA is given 5-10 mg daily for 10-14 days each month.
Surgical treatment: If patient karyotype includes a Y chromosome, streak gonads should be
removed to avoid the risk of malignant transformation (25%).
Oocyte donation: for women who want to achieve pregnancy, this is prohibited in Islamic countries.

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Chapter 2: Menstrual disturbance

Gonadal dysgenesis with normal Karyotype

(Pure gonadal dysgenesis)
one third of patients with gonadal dysgenesis.
It is likely due to single gene defects or destruction of gonadal tissue in utero, perhaps by
infection or toxins.
normal karyotype either 46,XX or 46,XY.
Patients with a 46,XY genotype are phenotypically female due to the lack of secretion of
testosterone and mllerian inhibiting substance by the dysgenetic testes (Swyer syndrome).
as Turner.

hidden menstruation due to the presence of genital tract outflow obstruction.

I. Inherited

Labial agglutination or fusion: due to female pseudohermaphroditism e.g. fetal congenital adrenal
hyperplasia (CAH) or luteoma of pregnancy.
Imperforate hymen: 1 in 2,000 women.
Transverse vaginal septum: 1 in 70,000 women.
Isolated atresia: of the vagina or cervix.
Non communicating horn: It accumulates menstrual blood.
II. Acquired

Cervical stenosis: This may result from conization, electrosurgery, or cryosurgery.

Cervical obstruction: by a mass.

Due to the presence of outflow obstruction, blood accumulates above the level of obstruction and
becomes thick and chocolate colored.
The sequence is hematocolpos, hematometra, hematosalpinx then pelvic hematocele which later
predisposes to endometriosis.
The main bulk of pelvi-abdominal mass is hematocolpos not hematometra.

Symptoms

Primary amenorrhea: is the main complaint, 2ry amenorrhea in acquired cases (rare).
Lower abdominal pain: cyclic in nature.
Abdominal swelling: by hematocolpos or full bladder.
Pressure symptoms: urinary frequency, dysuria, acute or chronic retention.

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Chapter 2: Menstrual disturbance

Fever and malaise: due to absorption of blood.
Signs

General examination: well developed secondary sexual characters.

Abdominal examination: Pelvi-abdominal mass that is tense, cystic, of limited mobility, and a solid
mass may be felt above it (the uterus).
Pelvic examination:
Vaginal examination:
Bulging bluish closed hymen if imperforate hymen.
A dimple with absent vagina if vaginal aplasia.
Rectal examination: cystic swelling compressing the anterior wall.
Investigations

Ultrasound: for diagnosis of non-communicating horn, hematocolpos, urological anomalies.

Laparoscopy: in case of non-communicating horn and other congenital anomalies.
IVP: for exclusion of urological anomalies which are common with mllarian anomalies.
Differential diagnosis

Pelvi-abdominal masses in cryptomenorrhea could be hematocolpos, full bladder due to chronic

retention or pelvic kidney.

Identification of the cause: by examination and investigations.

Treatment according to the cause:
Imperforate hymen:
Preoperative: Virginity certificate.
Operation: General anesthesia Cruciate incision under complete aseptic conditions
excision of the edges Blood is left to drain gradually to avoid splanchenic shock.
Postoperative: no drain is left.
Transverse vaginal septum:
If the septum i s thick: excision and skin grafting.
If the septum i s thin: excision and end to end anastomosis or Z-plasty.
Cervical atresia: trial for dilation.
Antibiotics: given pre-, intra- and postoperative, blood is a good medium for bacterial growth.

It is a syndrome of anterior pituitary necrosis due to severe postpartum hemorrhage. Pituitary necrosis
secondary to other causes is named (Simmonds disease)

Severe postpartum hemorrhage causes spasm of pituitary vascular supply which is already c ritical
because most of blood is shifted to the posterior pituitary at the time of labor for synthesis of oxytocin.

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Chapter 2: Menstrual disturbance

Defect

Clinical picture

Investigation
st

Deficient prolactin

Failure of lactation and breast atrophy (1 symptoms)

---

Deficient gonadotrophins

Secondary amenorrhea, genital atrophy, loss of lipido

Decreased FSH & LH

Hyopglycemia (& coma), hypotension, increased

Decreased ACTH

Deficient ACTH

susceptibility to infection, anaemia and theombocytobenia

Deficient TSH

Mental dullness, recent cold int olerance, hair falling

Decreased TS H

Deficient MSH

Pale waxy skin

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Treatment is only replacement, this includes:

Thyroxine: 130 g/day.
Cortisone: 15 mg/day.
Gonadotrophins: are given for ovulation induction in patients who want to get pregnant,
Clomiphene citrate is useless in those patients.

Frolish syndrome

A hypothalamic congenital disorder characterized by primary amenorrhea, obesity, infantile genital

organs and sleepiness.
Laurence-Moon-Biedl syndrome

It consists of the same features of Frolish syndrome but with also retinitis pigmentosa and blindness,
polydactyly and mental retardation.
Anorexia nervosa

It is a psychological disorder in which the patient has distorted body image and believes in being
obese. This results in abnormal food restriction and weight reduction, the patient is amenorrhic,
emaciated, and weak. This disorder requires psychotherapy.
Bulimia

It is a syndrome of overeating followed by self-induced vomiting or the use of laxative to avoid weight
again. Psychological therapy is needed.
Kallmann syndrome

Isolated GnRH deficiency along with olfactory affection (anosomia or hyposomia).

Lorian syndrome

For unknown cause, only growth hormone and gonadotrophins are affected and so the patient has
pituitary dwarfism along with amenorrhea and hypogonadism.
Empty sella syndrome

It is a congenital (or acquired following surgery, radiotherapy and infarction) syndrome of deficient dura
matter with herniation of the subarachnoid space into the sella turcica compression the pituitary.
Pseudocyesis

It is a syndrome resulting from either fear or strong desire to get pregnant, occurring usually above the
age of 40. It is hypothalamic mechanism with further suppression of FSH & LH.

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