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Menstrual DisordersDr.Ahmed RashadPGY2 Family Medicine

Under Supervision of Dr.Leena Kadhem

+Objectives

To understand the physiology of the normal menstrual cycle

To know definition and types of abnormal uterine bleeding

How to approach a case of abnormal uterine bleeding

Amenorrhea; types and causes

Dysmenorrhea; types and management

When to refer to secondary care

+Introduction

Menstrual disorders and abnormal uterine bleeding (AUB) are among the most frequent gynecologic complaints. [1]

Menstrual disorders frequently affect the quality of life of adolescents and young adult women and can be indicators of serious underlying problems.

+Normal Menstrual Cycle

The normal menstrual cycle is a tightly coordinated cycle of stimulatory and inhibitory effects that results in the release of a single mature oocyte from a pool of hundreds of thousands of primordial oocytes.

+H-P-O axis

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The average adult menstrual cycle is 28 days, with a range of 24 to 35 days , and lasts four to six days.

The median blood loss during each menstrual period is 30 mL; the upper limit of normal is 80 mL.

+CASE 1

A 35-year-old female presents to your office with concerns about heavy menstrual periods for the past year that occur at irregular intervals. She explains that sometimes her menses comes twice a month but other times will skip 2 months in a row. Her menses may last 7 to 10 days and require 10 to 15 thick sanitary napkins on the heaviest days. She admits to some fatigue, but she denies any lightheadedness. She has no pain with menses or intercourse. She denies any vaginal discharge or any other symptoms. She is a nonsmoker. She has had normal Pap smears in the past. She is in a stable monogamous relationship with her husband and denies a history of sexually transmitted infections (STIs). On physical examination, her blood pressure is 120/80 mmHg and her body mass index (BMI) is 32. Her physical examination is normal, including pelvic exam.

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The patient’s bleeding pattern is best described as …?

The most likely diagnosis is …?

What is the most likely underlying mechanism for

this patient’s abnormal bleeding?

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Abnormal Uterine Bleeding

+Definition

Abnormal uterine bleeding refers to uterine bleeding outside of the parameters noted below :

Duration greater than eight days

Flow greater than 80 mL/cycle or subjective impression of heavier-than-normal flow (ie, more than six full pads or tampons per day)

Occur more frequently than every 24 days or less frequently than every 38 days

Intermenstrual bleeding or postcoital spotting

Absence of menses

+ Oligomenorrhea: menstruation occurring with intervals of more

than 35 days

Polymenorrhea: menstruation occurring regularly with intervals of less than 21 days

Metrorrhagia: menstrual bleeding occurring at irregular intervals or bleeding between menstrual cycles

Menorrhagia: regular menstrual cycles with excessive flow (technically more than 80 mL of volume) or menstruation lasting more than 7 days

Menometrorrhagia: menstrual bleeding occurring at irregular intervals with excessive flow or duration

+Prevalence and Impact

In population-based studies, approximately 10 to 35 percent of women report having menorrhagia. [2-4]

Menorrhagia is a common reason for referral to a gynecologist .

Iron deficiency anemia develops in 21 to 67 percent of cases. [2]

Excessive and irregular bleeding can affect the quality of life. Absenteeism from work or school is bothersome to many women and bleeding may also interfere with sexual activity.

+Causes throughout Woman’s Lifetime

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Anovulatory Uterine Bleeding

+Pathophysiology Estrogen breakthrough bleeding

Anovulatory cycles have no corpus luteal formation. Progesterone is not produced. The endometrium continues to proliferate under the influence of unopposed estrogen.

Estrogen withdrawal bleeding

This frequently occurs in women approaching the end of reproductive life. Ovarian follicles in these women secrete less estradiol. Fluctuating estradiol levels might lead to insufficient endometrial proliferation with irregular menstrual shedding.

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+Causes

In Adolescents

Failure occurs secondary to delayed maturation of the hypothalamic-pituitary axis. Normal in 1-2 years after menarche.

Peri-menopausal

Anovulatory bleeding in menopausal transition is related to declining ovarian follicular function.

+ Approximately 6 to 10 percent of women with anovulation

have underlying polycystic ovary syndrome.

Uncontrolled diabetes mellitus, hypo- or hyperthyroidism, and hyperprolactinemia also may cause anovulation by interfering with the hypothalamic-pituitary-ovarian axis.

Antiepileptics (especially valproic acid [Depakene]) may cause weight gain, hyperandrogenism, and anovulation.

Use of typical antipsychotics (e.g., haloperidol), and some atypical antipsychotics (e.g. risperidone [Risperdal]) may contribute to anovulation by raising prolactin levels

+Evaluation

First, whom to evaluate ?

Patients with irregular cycles who should be evaluated include

a)adolescents with consistently more than three months between cycles or

b)those with irregular cycles for more than three years [3];

c)women who are likely perimenopausal and have increased volume or duration of bleeding over baseline.

+ Initial evaluation of anovulatory uterine bleeding should

include

a) Confirm a uterine source of bleeding on physical examination

b)Perform a pregnancy test.

c) Assess whether the woman is pre- or postmenopausal.

d)Evaluate the pattern, volume, and duration of blood loss.

+e) Assess ovulation:

• Ovulation can generally be documented clinically, based on regular cyclic menses with molimina (eg, breast tenderness, bloating or pelvic discomfort, mood changes, thin vaginal discharge), or

• can be confirmed by a serum progesterone level measured in the presumed luteal phase of the menstrual cycle; in most laboratories, a level of >4 ng/dL confirms ovulation.

f) Perform laboratory testing for anemia

g) Perform pelvic sonography to assess for uterine or other reproductive tract abnormalities that may contribute to uterine bleeding.

+g) ACOG recommends endometrial tissue assessment to

rule out cancer in

i. in adolescents and in women younger than 35 years with prolonged unopposed estrogen stimulation,

ii. women 35 years or older with suspected anovulatory bleeding, and

iii. women unresponsive to medical therapy

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Ovulatory Uterine Bleeding

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Ovulatory abnormal uterine bleeding, or menorrhagia, presents as bleeding that occurs at normal, regular intervals but that is excessive in volume or duration.

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Etiologies

+Bleeding disorders

Suspected if :

i.Menorrhagia since menarche

ii.Family history of bleeding disorders

iii.Personal history of 1 or more of the following:• Notable bruising without known injury• Bleeding of oral cavity or gastrointestinal tract without

obvious lesion• Epistaxis greater than 10 minutes duration (possibly

necessitating packing or cautery.

+CASE 2

A 27-year-old nulligravida female presents to your office for routine exam. Upon gynecological history, you discover that she has a 5-year history of oligomenorrhea, with only approximately two or three menses a year. She denies intercycle spotting or premenstrual symptoms. Her last menses was 3 months ago. Her blood pressure is 120/75 mmHg and her BMI is 34. Her physical exam reveals a moderate amount of facial hair and facial acne. Her pelvic examination is unremarkable

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What condition do you suspect in this patient?

What are the treatment options ?

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Amenorrhea

+Definition and types

Primary amenorrhea is defined as the absence of menses at:

i. age 16 in the presence of normal growth and secondary sexual characteristics, or

ii. age 14, if no menses have occurred and there is an absence of secondary sexual characteristics.

Secondary amenorrhea is the absence of menses for three months in women with previously normal menstruation and for nine months in women with previous oligomenorrhea.

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Primary Amenorrhea

+Etiology of 1ry AmenorrheaHypothalamic and Pituitary causes

①Functional hypothalamic amenorrhea.

•Abnormal hypothalamic gonadotropin-releasing hormone (GnRH) secretion decreased gonadotropin pulsations

i.absent LH surges

ii.absence of normal follicular development

iii.anovulation.

•Multiple factors may contribute to the pathogenesis of functional hypothalamic amenorrhea, including eating disorders (such as anorexia nervosa), exercise, and stress

+② Congenital GnRH deficiency or idiopathic

hypogonadotropic hypogonadism

Kallmann’s Syndrome ?

③ Constitutional delay of puberty

• characterized by both delayed adrenarche and gonadarche.

④ Hyperprolactinemia

+Ovarian Causes

①Gonadal dysgenesis

②Turner syndrome

③Polycystic ovary syndrome

④Premature ovarian failure

•Loss of ovarian function before age of 40

•Idiopathic, but maybe related to a variant gene.

+Polycystic Ovarian Syndrome

+Congenital disorders of the uterus and vagina

①Müllerian agenesis causes approximately 15 percent of primary amenorrhea.[4]

②Imperforate hymen

③Transverse vaginal septum

+Diagnosis

History

Detailed history of pubertal development

Family history of menarche, pubertal development

History of weight loss, stress, exercise (athletic activity)

Detailed dietary history

History of contraception, medications

History suggestive of CNS disease (eg, headaches, visual changes)

History of chronic illnesses (eg, Crohn disease)

+Physical examination

Height, weight, and growth charts

Breast development, pubic hair

Syndromic appearance (eg, short stature, webbed neck)

Visual fields, thorough neurologic examination, optic fundi

Evidence of hyperandrogenism (eg, acne, hirsutism, clitoromegaly)

Evidence of thyroid disease

Evidence of chronic illnesses

Evidence of pregnancy

+Evaluation

Primary amenorrhea is evaluated most efficiently by focusing on the

a)presence or absence of breast development (a marker of estrogen action and therefore function of the ovary),

b)the presence or absence of the uterus (as determined by ultrasound, or in more complex cases by magnetic resonance imaging)

c)and the follicle-stimulating hormone (FSH) level.

+Etiology of 2ry Amenorrhea PREGNANCY is the most common cause of

secondary amenorrhea.

Hypothalamic dysfunction

① Functional hypothalamic amenorrhea

② Inflammatory or infiltrative diseases (eg.Lymphoma)

③ Brain tumors (i.e. Craniopharyngioma)

④ Cranial irradiation

⑤ Pituitary stalk dissection or compression

+ Pituitary dysfunction

① Hyperprolactinemia • Prolactinomas account for 20% of secondary

amenorrhea• Account for 90% of secondary amenorrhea due to

pituitary problems

② Pituitary tumors• Acromegaly• Corticotroph adenomas (i.e. Cushing’s disease)• Meningioma (of the sella), germinoma, glioma

③ Empty sella syndrome

④ Pituitary infarct/pituitary apoplexy• Sheehan’s syndrome

+ Ovarian dysfunction

•Menopause: defined as 12 months of amenorrhea in a woman over age 45 in the absence of other biological or physiological causes.

•Premature ovarian failure

•Surgical removal

•Polycystic ovarian disease

+ Uterine causes

① Acquired scarring of the endometrium

• due to instrumentation e.g. Asherman’s Syndrome• due to infection eg. tuberculosis

① Cervical stenosis, often due to instrumentation

+Prolactin ≤ 100 ng per mL (100 mcg per L)Altered metabolismLiver failureRenal failureEctopic productionBronchogenic (e.g., carcinoma)Breastfeeding

Prolactin > 100 ng per mLEmpty sella syndromePituitary adenoma

+CASE 3

A 15-year-old nulligravida female presents with her

mother for evaluation of painful periods. Menarche was

at age 14. Her periods are typically every 4–8 weeks and

are very painful. She has missed 1–2 days of school with

each menses because of the severe pain and has been

suspended from the volleyball team because of missed

practices. She denies intercourse. She has never had a

pelvic examination. Her review of systems is otherwise

negative.

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What is the MOST likely etiology of her

irregular cycles?

What is the etiology?

What is the best first-line treatment for this

patient?

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Dysmenorrhea

+Definition and types

Dysmenorrhea is defined as difficult menstrual flow or painful menstruation. It is one of the most common gynecologic complaints in young women who present to clinicians.[5]

Dysmenorrhea can be divided into 2 broad categories: primary (spasmodic) and secondary (congestive).

+Primary dysmenorrhea

Primary dysmenorrhea is defined as menstrual pain that is not associated with macroscopic pelvic pathology.

It typically occurs in the first few years after menarche[6]and affects as many as 50% of postpubertal females.

In an epidemiologic study of an adolescent population (age range, 12-17 years), reported that dysmenorrhea had a prevalence of 59.7%. [7]

+Risk factors

Early age at menarche (< 12 years)

Nulliparity

Heavy or prolonged menstrual flow

Smoking

Positive family history

Obesity

+Pathophysiology

Current evidence suggests that the pathogenesis of primary dysmenorrhea is due to prostaglandin F2α (PGF2α), a potent myometrial stimulant and vasoconstrictor, in the secretory endometrium. [8]

+Treatment

Treatment is directed at providing relief from the cramping pelvic pain and associated symptoms .

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the best-established initial therapy for dysmenorrhea. [9] They decrease menstrual pain by lowering prostaglandin F2α (PGF2α) levels in menstrual fluid.

Oral Contraceptives also relieve symptoms, particularly if contraception is required.

+Secondary dysmenorrhea

Less common than primary dysmenorrhea

It is associated with pelvic pathology

It tends to occur several years after the menarche

The woman may complain of a change in the timing and intensity of her pain

The pain may last throughout menstruation

The pain may be associated with discomfort before the onset of menstruation.

+Causes

Leiomyomata (fibroids)

PID

Tubo-ovarian abscess

Endometriosis

+Management

Treatment of secondary dysmenorrhea involves correction of the underlying organic cause.

Specific measures (medical or surgical) may be required to treat pelvic pathologic conditions (eg, endometriosis) and to ameliorate the associated dysmenorrhea

+Resources [1] Caufriez A. Menstrual disorders in adolescence: pathophysiology and treatment. Horm Res 1991; 36:156.

[2]Côté I, Jacobs P, Cumming DC. Use of health services associated with increased menstrual loss in the United States. Am J Obstet Gynecol 2003; 188:343.

[3]Santer M, Warner P, Wyke S. A Scottish postal survey suggested that the prevailing clinical preoccupation with heavy periods does not reflect the epidemiology of reported symptoms and problems. J Clin Epidemiol 2005; 58:1206.

[4]Shapley M, Jordan K, Croft PR. An epidemiological survey of symptoms of menstrual loss in the community. Br J Gen Pract 2004; 54:359.

[3] Speroff L, Fritz MA. Amenorrhea. In: Clinical gynecologic endocrinology and infertility. 7th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins, 2005;401–64.

[4] ACOG Committee on Practice Bulletins—Gynecology. American College of Obstetricians and Gynecologists. ACOG practice bulletin: management of anovulatory bleeding. Int J Gynaecol Obstet. 2001;72(3):263–271.

[5] Hallberg L, Högdahl AM, Nilsson L, Rybo G. Menstrual blood loss--a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand 1966; 45:320.

[6]Diaz A, Laufer MR, Breech LL; American Academy of Pediatrics Committee on Adolescence, American College of Obstetricians and Gynecologists Committee on Adolescent Health Care. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006;118(5):2245–2250.

[[7] Klein JR, Litt IF. Epidemiology of adolescent dysmenorrhea. Pediatrics. Nov 1981;68(5):661-4

[8] Willman EA, Collins WP, Clayton SG. Studies in the involvement of prostaglandins in uterine symptomatology and pathology. Br J Obstet Gynaecol. May 1976;83(5):337-41

[8] Slap GB. Menstrual disorders in adolescence. Best Pract Res Clin Obstet Gynaecol 2003; 17:75.

[9] Proctor M, Farquhar C. Dysmenorrhoea. Clin Evid. 2002;(7):1639–53.

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