ENDOMETRIOSIS, ADENOMYOSIS, DYSMENORRHEAGYNE ENDOMETRIOSIS, ADENOMYOSIS, DYSMENORRHEAMedical management: GnRH Agonist

- Specific suppression of gonadotrophin secretion down regulation & desensitization of the pituitary to produce extremely low levels of circulating estrogen

- Secondary diminution of ovarian steroidogenesis- Since endometrial tissue requires estrogen to grow,

endometriosis is temporarily halted- Induce temporary menopause by blocking estrogen production- Mainstay of endometriosis treatment today

GnRH agonist (Examples)- Leuprolide acetate (Lupron, injectable)o 3.75 – 7.5 mg IM per month

- Nafarelin acetate (Synarel, intranasal)o One spray (200 ug) in one nostril - AM, the other nostril – PM

- Goserelin acetate (Zoladex, subcutaneous implant)o 3.6 mg every 28 days

- Chronic use produces “medical oophorectomy” o (pseudomenopause or medical castration)

- Side effects: primarily associated with estrogen deprivation similar to menopauseo Hot flushes, vaginal dryness, insomnia

Reversible after discontinuing therapy – ovarian function will return to normal 6 – 2 weeks after 6 months of therapy

o No effect on sex hormone – binding globulins- No androgenic side effects- No significant changes in serum cholesterol, HDL or LDL- Currently, clinicians “add – back” therapyo Very low doses of estrogen (30 pg/ml of estradiol)o Low doses of progestins

- Both E & Po Begun after 2 – 3 months of GnRH agonist therapyo Makes side effects less bothersome without compromising the

agonist’s therapeutic effect o Diminish demineralization of bone (osteoporosis)

Medical management: Oral contraceptives- Monophasic oral contraceptive taken CONTINUOUSLY & not

intermittently- Amenorrhea is the desired end point in the therapy- Prolonged therapy causes endometrial gland & marked decidual

reaction of the stroma

Medical management: Other hormonal treatment- Progestins

Prolonged amenorrhea (endometrial atrophy)o Medroxyprogesterone acetate (MPA)

30 mg orally per dayo Depomedroxyprogesterone acetate (DMPA)

150 mg IM every 3 monthso Gestrinone

2.5 – 7.5 mg per week taken orally- RU 486

o Antiprogestin agent used to produce amenorrhea

Surgical therapy: ENDOMETRIOSIS- The foundation of treatment for MODERATE TO SEVERE

Endometriosis- Mandatory for:o Acute rupture of large endometriomaso Ureteral obstructiono Intestinal obstructiono Ovarian endometriomas > 2 cm.o Adnexal enlargements > 8 cm.

- Surgical management o Diagnosiso Therapeutic

- LAPAROSCOPYo Preferred surgery; shorter recovery period and reduction in

the extent of subsequent adhesions- LAPAROTOMY

Surgical therapy – ConservativeGOAL: restore the anatomy & physiology

- Removal of all macroscopic, visible areas of endometriosis with preservation of ovarian function

- Removal or destruction of implants- Removal of endometrioas- Lysis of adhesions- Resection of the utero – sacral ligaments- Presacral neurectomyo Relieves midline pain (dysmenorrheal & dyspareunia) onlyo Does not diminish pain in other areas of the pelvic

Surgical therapy: ENDOMETRIOSIS- Definitive surgery- TAH, BSO & removal of all visible endometriosis reserved foro Far – advanced diseaseo For whom fertility is NOT a considerationo Patients with pain that continues after medical & conservative

surgery

ADENOMYOSIS- ENDOMETROSIS INTERNAo Derived from aberrant glands of the basalis layer of the

endometriumo Usually diagnosed incidentally by the pathologist on histologyo Histogenesis of adenomyosis is DIRECT EXTENSION from the

endometrial lining

Pathology: ADENOMYOSIS- 2 distinct pathologic presentationo Diffuse involvement of both anterior & posterior walls of the

uterus Posterior wall is more involved The individual areas are not encapsulated

o Focal area or adenomyoma Results in asymmetric uterus May have a pseudocapsule

- Diagnostic criterion:o Endometrial glands & stromas more than one low- powered

field from the basal year of the edometrium- Hyperplasia & Hypertrophy of the myometriumo Produces the globular enlargement of the uterus

Clinical Diagnosis: ADENOMYOSIS- CLASSIC SYMPTOMS:o Secondary dysmenorrheal

Dyspareuniao Menorrhagiao Infertility

- Secondary dysmenorrhealo Become increasingly severe

When the gland tissue grows during the menstrual cycle and then at menses tries to slough, the old tissue and blood cannot escape the uterine muscle and flow out of the cervix as part of normal menses.

This trapping of the blood and tissue causes uterine pain in the form of monthly menstrual cramps

o Dyspareunia Midline in location, deep pain in the pelvis

o Menorrhagia Produces abnormal uterine bleeding when some of the

blood finally escapes the muscle resulting in prolonged menstrual flow

Definitive diagnosis: ADENOMYOSIS- Diagnosis is confirmed following histologic examination of a

hysterectomized uteruso Retrospective diagnosis

Pelvic Exam: ADENOMYOSISRarely causes uterine enlargement greater than 14 weeks size

ENDOMETRIOSIS, ADENOMYOSIS, DYSMENORRHEA- Enlargement uterus is soft or squishy to the feel- A sonogram (ultrasound)and laparoscopic evaluation may also be

helpful in making the diagnosis- MRI’s can often identify adenomyosis- Examination of the surgical specimen under a microscope is the

only method to make an absolute diagnosis of adenomyosis

Management: ADENOMYOSISThe treatment options for adenomyosis are similar to those of endometriosis:

1. Observation – If the symptoms are not severe2. Medical treatment:

- Birth control pills- GnRH agonists – will temporarily alleviate the symptoms and

reduce the size of the adenomyosiso Will not eliminate the adenomyosis nor prevent continued

growth once the GnRH is discontinued

Conservative surgical treatment- Indications:o A woman who is trying to get pregnanto A single well defined adenomyosiso A woman who does not want a hysterectomy and does not

mind undergoing repeated surgeries- Removal of the adenomyosis and preserve the uterus –

impossible- Adenomyomectomyo Removal of the adenomyosis with recontraction of the uterus

will reduced the amount of adenomyosis present

DysmenorrheaDefinition:

- A severe, painful cramping sensation in the lower abdomen often accompanied by other biologic symptoms, all occurring just before or during the menses such as:o Sweating, tachycardia, headaches, nausea, vomiting, diarrhea,

and tremulousnessPrimary dysmenorrhea

The term refers to pain with no obvious pathologic pelvic disease Primary dysmenorrheal almost always first occurs in women

younger than 20 Indeed, the patient will report pain as soon as she establishes

ovulatory cycles These patients are suffering from the effects of endogenous

prostaglandins

Secondary dysmenorrhea Is associated with pelvic conditions or pathology that causes

pelvic pain in conjunction with the menses May occur in women younger than 20, but it is most often seen in

women older than 20

Incidence of Dysmenorrhea Wide range (16-90%) average 75% Mildo No systemic symptoms, medication rarely required, work rarely

affected Moderateo Few systemic symptoms, medication required, work

moderately affected Severeo Multiple symptoms, poor medication response, work inhibited

Less likely to have dysmenorrhea are: Women who had vaginally delivered a childo Pregnancy itself without actual birth did not seem to alleviate

dysmenorrhea As women who had ectopic pregnancies or spontaneous or

voluntary terminations of pregnancy were not relieved of their symptoms

Smokers were less likely to have dymenorrhea Users of oral contraceptive (OC)

Family historyo Increased among mothers and sisters of women with

dysmenorrhea

Pathogenesis of Primary dysmenorrhea Associated between elevated prostaglandin F2a (PG F2a) levels in

the secretory endometrium and the symptoms of dysmenorrhea, including:o Uterine hypercontractilityo Complaints of severe crampingo Other prostaglandin – induced symptoms

Arachidonic acid:o Increased amounts in the uterus during ovulatory cycleso The precursor to prostaglandin productiono Converted to PG F2a, PGE2, and leukotrienes

Which are involved in increasing myometrial contractions During menses contractions decrease uterine blood flow and

cause ischemia and sensitization of pain fiberso Ultrasound & MRI have correlated dysmenorrheal with

myometrial changes and decreased blood flowo PG F2a and PGE2 affect other organs such as the bowel and

result in nausea, vomiting and diarrhea During menses these contractions decrease uterine blood flow

and cause ischemia and sensitization of pain fibers Mechanisms contributing to generation of pain in primary

dysmenorrheal

Diagnosis of primary dysmenorrheaThe diagnosis is made by the history & PE

Midline, cramping lower abdominal paino Begins with the onset of menstruation

May be severe pain and also involve the low back and thighs Gradually resolves over 12 to 72 hours Pain does not occur at times other than menses

Physical exam With primary dysmenorrheal have a normal pelvic exam

Treatment of primary dysmenorrheal Nonsteroidal anti-inflammatory drugs (NSAIDs)o Prostaglandin synthetase inhibitors (PGSI)o Demonstrated to alleviate these symptoms of primary

dysmenorrhealo These substances are nonsteroidal and anti- inflammatory

Two chemical groups of PG inhibitors: Arylcarboxylic acids:o Acetylsalicylic acid (aspirin) o Fenamates (mefenamic acid)

Arylalkanoic acids:o Arylpropinoic acids (ibuprofen, naproxen)o Indoleacetic acids (indomethacin)

Treatment of primary dysmenorrheal Cyclooxygenase (COX-2) inhibitorso Ex. Celecoxibo COX-2 expression in the uterine glandular epithelium was

maximal during menstruation Suggesting a possible association with the cause The increased expression of COX-2 was eliminated with

continuous use of OCs which are also an effective treatment The specific effect of COX-2 inhibitors on the uterine musculature

is:o Reduction of the contractility as measured by reduction of

intrauterine pressure

Side effects of NSAIDs & COX-2 inhibitors Minimal NSAIDs –associated side effects involving theo Central nervous system (CNS)o Gastrointestinal tracto Allergy to ASA & NSAIDs

COX-2 inhibitors

ENDOMETRIOSIS, ADENOMYOSIS, DYSMENORRHEAo Serious adverse cardiovascular events

Other treatment modalities Oral contraceptives o OCs will relieve the symptoms of primary dysmenorrheal in

about 90% of patientso OCs suppress ovulation and endometrial proliferationo OCs progestin component blocks the production of

prostaglandin formationOther therapy

Progestaserto Reduce menstrual pain in women

Microwave endometrial ablation with transcervical resection of the endometrium for menorrhagia o Showed both techniques reduced menstrual pain

Transcutaneous electrical nerve stimulation (TENS)o More effective than placebo in relieving dysmenorrheal

although this was not as effective as analgesicso Relieved menstrual pain without reducing intrauterine pressure

Presacral neurectomyo Surgical managemento Last resort in the management if all treatment modalities fail

Secondary Dysmenorrhea Pelvic disease should be considered in case that do not respond to

NSAIDs and OCs for presumed primary dysmenorrheal Group of pelvic problems that includeo Cervical stenosiso Ectopic endometrial tissueo Pelvic inflammationo Pelvic congestion o Conditioned behavior

Cervical stenosis Severe narrowing of the cervical canalo At the level of the internal oso Impede menstrual flow causing an increase in intrauterine

pressure at the time of menses Retrograde menstrual flow through the fallopian tubes into the

peritoneal cavity may take place Thus severe cervical stenosis may eventually be associated with

pelvic d as well

Etiology: cervical stenosis Congenital Secondary to cervical injuryo Electrocautery, cryocautery or operative trauma(l.e. conization)o From an inflammatory process caused by infectiono The application of caustic substances

Hypoestrogenismo After any of these conditions the cervical canal may narrow

because of contraction of scar tissueHistory

Cervical stenosis should be consideredo History of scant menstrual flow o If severe cramping continues throughout the menstrual periodo A hematometria or pyometria may occur

DiagnosisPelvic exam

- Scarring of the external os- Impossible to pass a pap smear brush or uterine sound through

the internal os during the proliferative stage of the menstrual cycle

Diagnosis is generally documented- By the inability to pass a thin probe of a few millimeter diameter

through the internal os- By hysterosalpingogram ( thin stringy appearing canal if

hysteroscopy end )- D&C – difficult to pass a thin probe into the internal os

Treatment: cervical stenosis Dilating the cervix by D&C

- Progressive dilator- Progressive use of Laminaria japonica tent

: Unfortunately, cervical stenosis often recurs after therapy, necessitating repeat procedures

Pregnancy and vaginal delivery often afford a more lasting cure

Pelvic inflammation Gonorrhea, Chlamydia, or other infections

- May cause pelvic inflammation or pelvic abscess.- Healing may be associated with pelvic adhesions and tubal

damage that may cause pelvic pain

Pelvic inflammatory disease (PID) can lead to chronic pelvic pain in up to 30% of women.

- May be aggravated at menses, causing dysmenorrheal.

Other Pelvic InflammationInfections secondary

- Appendicitis- IUD use, may also create a similar response.o The pain may be secondary to the congestion and edema that

occur normally at menses, which may subsequently be aggravated by the healed inflammatory areas and adhesions.

pelvic pain – usually burning or throbbing in nature, worse at night and worse after standing.

Pelvic congestion syndrome- results from engorgement of pelvic vasculature.

Physical examination of the vagina and cervix usually reveals vasocongestion with evidence of some uterine enlargement and tenderness..

Diagnosis: Pelvic Congestion syndromeMade by:

- Observation of the features noted - Laparoscopyo Rules out other cause of pelvic paino Demonstrates congestion of the uterus and engorgement or

variscosities of the broad ligament and pelvic side wall veins.

Diagnostic Laparoscopy: Pelvic Congestion syndrome- Observe the broad ligament vasculature as the pressure of the

carbon dioxide or nitrous oxide is releasedo At full pressure during the procedure these vessel may be

obliterated but will reappear as pressure is reduced

Treatment: Pelvic Congestion syndrome- No standard therapeutic approach is availableo Ovarian hormone suppressiono Local sclerotherapy (for vulvar varices)o Embolization of the hypogastric veino Resection of the gonadal veino Hysterectomy

Other causes – secondary dysmenorrheal- Leiomyomas or polyps at the junction of the internal os and lower

uterine segmento May produce a valve-like effect at the os at the time of menseso Become engorged or edematous at the time of menses,

accentuating the problemOther causes

- Diagnosis of leiomyomas or polyps by:o Historyo Hysterosalpingographyo Hysteroscopyo D&C

- Therapy consists of:o Excising the pathologic tissueo Myomectomy or hysterectomy may be necessary

ENDOMETRIOSIS, ADENOMYOSIS, DYSMENORRHEAPremenstrual syndrome (PMS)

- A group of mild to moderate symptoms, both physical and behavioralo Occur in the second half of the menstrual cycle ando May interfere with work and person relationships.o Followed by a period entirely free of symptoms.

Premenstrual Dysphoric Disorder (PMDD)- Represents a more severe disorder with marked behavioral

emotional symptoms.- PMS differs from PMDD in severity of symptoms, and women with

PMDD must have one sever e affective symptoms.Symptoms:

o Markedly depressed mood hopelessnesso Anxiety or tensiono Affective lability, oro Persistent angero Multiple physical symptoms may also be present.

- PMDD also differs from PMS as there is substantial impairment in personal functioning.

- PMS and PMDD are similar in that the symptoms manifest in the luteal phase of the menstrual cycle and resolve during menses.

Symptoms- Somatic symptomso Related to abdominal bloating, breast tenderness, and various

pain constellations such as headache.- Psychological symptoms varyo From fatigue, irritability, and tension to anxiety, labile mood

and depression- Consistency of symptoms was found over two consecutive cycles,

especially for emotional symptoms.

PMS/PMDD etiology- Ovulationo Seems to cause alterations in neurohormones and

neurotransmitters that lead to reduction of serotonergic function during the luteal phase.

- The most effective evidence-based treatment for moderate to severe PMS and PMDD symptoms are SSRIs and agents that block ovulation.

Drug Management PMS/PMDD- Therapy with psychoactive drugso The selective Serotonin Reuptake Inhibitors (SSRIs)o Extremely effective for treating PMS o First-line treatment for PMDD.