Endometriosis + PCOS

What is endometriosis?

Endometriosis is a chronic condition characterized by the growth of hormone-responsive endometrial tissue outside the uterine cavity

Where are ectopic endometriotic implants found?

Typically, found on the peritoneal surface, within the ovary or invading the rectovaginal septum

• Can be found in other regions

What is the overall prevalence of endometriosis?

among reproductive-age people is around 10% (190 million)

What is endometriosis often followed up with?

Accompanied by pelvic pain or infertility in up to 90 million persons worldwide

What are the social symptoms associated with endometriosis?

Work absenteeism, social isolation, and high costs of therapy

What is the stats of having endometriosis?

one in ten

What is endometriosis network canada dedicated to?

to providing education, awareness, hope, and support services for individuals with #Endometriosis

What is the experience of pain and cramps for those with endometriosis?

• Those with endometriosis typically describe menstrual pain that is far worse than usual

• Tend to report that the pain increases over time

Is the severity of pain a reliable indicator?

▸The severity of the pain isn't necessarily a reliable indicator of the extent of the condition

▸Some people with mild endometriosis have intense pain, while others with advanced endometriosis may have little pain or even no pain at all

What are common sign and symptoms of endometriosis:

▸Painful periods (dysmenorrhea). Pelvic pain and cramping may begin before a period and extend several days. There can be lower back and abdominal pain.

▸Pain with intercourse. Pain during or after sex is common with endometriosis.

▸Pain with bowel movements or urination. Most likely to experience these symptoms during a period.

▸Excessive bleeding. Occasional heavy periods (menorrhagia) or bleeding between periods (menometrorrhagia).

▸Infertility. Endometriosis is first diagnosed in some people who are seeking treatment for infertility.

▸Other symptoms. The experience of fatigue, diarrhea, constipation, bloating or nausea, especially during menstrual periods.

What are some other symptoms prominent during mensuration?

The experience of fatigue, diarrhea, constipation, bloating or nausea, especially during menstrual periods.

What is the relationship between fertility and endometriosis?

Endometriosis is first diagnosed in some people who are seeking treatment for infertility.

What is the Excessive bleeding?

Occasional heavy periods (menorrhagia) or bleeding between periods (menometrorrhagia).

What is menorrhagia

Occasional heavy periods

What is menometrorrhagia

bleeding between periods

What is Pain with bowel movements or urination?

Most likely to experience these symptoms during a period.

What are Painful periods (dysmenorrhea)?

Pelvic pain and cramping may begin before a period and extend several days. There can be lower back and abdominal pain.

What are Pain with intercourse?

Pain during or after sex is common with endometriosis.

What is dysmenorrhea?

Painful periods

Where are the most common sites of endometrosis?

▸ The ovaries

▸ The fallopian tubes

▸ Ligaments that support the uterus (uterosacral ligaments)

▸ The posterior cul-de-sac, i.e., the space between the uterus and rectum

▸ The outer surface of the uterus

▸ The lining of the pelvic cavity

Where else can you find endometrial tissue?

▸ The intestines

▸ The rectum

▸ The bladder

▸ The vagina

▸ The cervix

▸ The vulva

What is the current gold standard for diagnosis?

Direct visualization of endometriotic implants is the current gold standard for diagnosis

Where are superficial lesions found?

lesions are found on the peritoneal or ovarian surfaces.

How do superficial lesions appear?

• appear dark blue or brown =hemosiderin content

• non-pigmented lesions= usually white in colour and may show vesicular or fibrotic appearances.

What is Haemosidren?

When red blood cells break down and start to release iron

What is a vesicle?

Small fluid-filled sac in the body

What is a fibrotic?

The formation of an abnormal amount of fibrous tissue

What is a laparoscopy?

• A small telescope (laparoscope) is inserted into the abdomen to look directly at the internal tissue.

• Laparoscopies are always carried out under general anesthetic.

What can you do alongside a laparoscopy

Various procedures can be performed in order to destroy or remove the endometriosis, endometriotic cysts and release scar tissue (adhesions).

What were physicians taught that endometrial implants were?

▸ Physicians were taught that endometriosis implants were blue-black “powder burns” or “mulberry lesions”.

▸ In recent years, several stages of implant development have been appreciated, each with a corresponding appearance.

What is the variety of early lesions of implants appear as?

Can appear as papular excrescences (solid mass) or vesicles, and can range in colour from clear to bright red.

What are lesions in phase with eutopic endometrium?

• About one third of lesions are in phase with the eutopic endometrium and have a tendency to spontaneously grow and regress.

• This characteristic suggests a fluctuating proliferation in association with hormone production during the menstrual cycle.

What are endometriomas?

-Cysts that form in the ovaries when the same kind of tissue that grows in the uterus (endometrium).

-These cysts fill with blood as they grow.

-The blood turns into a dark brown fluid, so endometriomas are sometimes called “chocolate cysts.”

-Endometriomas can cause pain and discomfort, as well as scarring and damage to the ovaries.

Generally what is classification of stages based on?

Is based on the location, amount, depth, and size of the endometrial implants.

What does each stage mean?

1. Stage I is minimal

2. Stage II is mild

3. Stage III is moderate

4. Stage IV is severe.

What is the aspects of criteria to determine endometrial implants severity?

[1] Extent of the spread of the implants

  [2] Involvement of pelvic structures in the disease

  [3] Extent of pelvic adhesions

  [4] Blockage of the fallopian tubes

What are the 3 theories on how endometriosis began?

1. Retrograde or Reflux menstruation

2. Coelomic Metaplasia

3. Lymph & vascular metastasis

What is the Retrograde or Reflux menstruation theory?

▸ Endometriosis derives from the reflux of endometrial fragments regurgitated through the fallopian tubes during menstruation with subsequent implantation on the peritoneum and the ovary.

What is the steps of retrograde menstruation?

1. Endometrial cells in menstrual fluid reach the peritoneal cavity

2. Once adhesion invasion occurs, activation and infiltration of inflammatory and immune flow

3. After cell growth, angiogenesis and antiapoptosis occurs

4. Leads to secretion of prostaglandins, estradiol

5. Finally causing fibrosis scarring pain

What is a summary of steps that occur during retrograde menstruation?

Proposed establishment of peritoneal endometriotic implants via retrograde menstruation, attachment, proliferation, migration, neovascularization, inflammation, and fibrosis.

How was prostaglandin initially discovered?

Two gynecologists discovered that human semen contains a substance that causes contraction of the human uterus

• discovered that the active substance in semen was fat soluble

Why was prostaglandin given that name?

• Named prostaglandin because it was thought to be secreted by the prostate gland into semen

• The seminal vesicles are the major source of prostaglandins

Where are prostaglandins produced?

Are produced in every tissue of the body

Where are prostaglandins made and why?

Are made at sites of tissue damage or infection, where they cause inflammation, pain and fever as part of the healing process

What is coelomic metaplasia?

- a committed cell type (e.g., mesothelium) trans-differentiates into an alternative cell type (e.g., endometrial epithelium).

• reprogramming of mesenchymal stem cells may be involved

What are other clinical examples of metaplasia?

-Barrett’s esophagus, where bile acids transform stratified squamous esophageal cells into mucin-containing goblet cells

-And in the lung, where columnar tracheobronchial epithelium can be induced by cigarette smoking to undergo squamous differentiation

What is the lymph & vascular metastasis theory/

▸The metastasis theory hypothesizes that menstrual tissue travels from the endometrial cavity to lymph nodes and from there through lymphatic channels and veins to distant sites.

Where did the lymph and vascular metastasis theory begin from?

Endometriosis has also been identified in sites distant from the pelvis, including abdominal lymph nodes, lungs, pleura, spinal cord, and even in the nose.

What reagents are responsible for the pain during endometriosis?

▸Endometriotic implants secrete estradiol (E2) as well as prostaglandin E2 (PGE2 ), agents that attract

-macrophages,

-neurotrophic peptides,

-enzymes for tissue remodelling,

-and tissue inhibitors,

and proangiogenic substances.

Why can endomteriosis be so painful?

They are infiltrated by sensory, sympathetic, and parasympathetic nerves and elicit an inflammatory response

Peritoneal endometriosis can also release what?

aromatase which means

can release estrogen as seen in this

What does Nonsteroidal anti-inflammatory drug help with?

Dysmenorrhea

What does oral contraceptives help with?

Dysmenorrhea

What does aromatase inhibitors help with and what can be a problem?

Helps as a Third line: Dysmenorrhea, chronic pelvic pain

Can Cause: Hypoestrogenism (because aromastse is not active)

What does GnRH agonist help with and what can be a problem?

Helps as a third line: Dysmenorrhea, chronic pelvic pain

Can Cause: Hypoestrogenism because more GnRH creates a negative feedback loop

Why is estrogen related to pain here

it can cause proliferation of implanted tissue which cna cause pain

What is March?

March is endometriosis and PCOS

What is PCOS?

A variable disorder that is marked especially by amenorrhea, hirsutism, obesity, infertility, and ovarian enlargement and is usually initiated by an elevated level of luteinizing hormone, androgen, or estrogen which results in an abnormal cycle of gonadotropin release by the pituitary gland  

What is PCOS also referred to as?

Called also polycystic ovary disease, polycystic ovary syndrome, Stein-Leventhal syndrome

Where can dysmenorrhea pain be felt?

iThe pain is typically cramping in nature and may be felt in the lower abdomen, back, or thighs.

What does it mean if dysmenorrhea is primary?

Meaning that there is no underlying medical condition causing the pain

What does it mean if dysmenorrhea is secondary?

which means that it is caused by a medical condition, such as endometriosis or uterine fibroids.

What are options for dysmenorrhea treatment?

May include over-the-counter pain medications, hormonal birth control, or other prescription medications.

What if a functional cyst?

• The most common type of ovarian cyst is called a functional cyst.

• These cysts are described as "functional" because they often develop during the menstrual cycle

What are follicular cysts?

• These usually go away on their own in 1 to 3 months.  

• These form when an egg doesn't release as expected, so the follicle keeps growing.

What are corpus luteum cyst?

These also usually go away on their own.

• These form after the follicle ruptures at ovulation.

• The follicle reseals and fluid starts to buildup within it.

• They can enlarge and cause pain, bleed, or twist the ovary.

What are the two types of functional cyst?

1. Follicular

2. Corpus Luteum cysts

What are 2 other forms of cysts then functional??

can also be related to endometriosis

• formed from the outer surface of the ovary (cystadenomas)

• formed with non-ovarian tissue (dermoid cysts)

Is PCOS a common endocrine disorder?

• PCOS is the most common endocrine disorder in reproductive aged people

• With a prevalence between 5% and 15%, depending on the diagnostic criteria applied

What is the relationship between familial occurrence and PCOS ?

• It has been well documented that PCOS tends to aggregate within families

• In a study of 115 sisters of 80 probands, PCOS was demonstrated in 22% of reproductive-aged siblings whereas hyperandrogenemia was found in an additional 24%.

What genome-wide association?

• Studies are a relatively new way for scientists to identify genes involved in human disease

What does genome-wide association tell us?

• For small variations, called single nucleotide polymorphisms or SNPs, that occur more frequently in people with a particular disease than in people without the disease

• Each study can look at hundreds or thousands of SNPs at the same time

What is the use of SNPS study?

▸Each study can look at hundreds or thousands of SNPs at the same time

▸Researchers use data from this type of study to pinpoint genes that may contribute to a person’s risk of developing a certain disease

What is the the basic characteristics of PCOS?

A familial heterogeneous disorder of reproductive-aged people characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovary morphology

Do we know the molecular basis for PCOS?

Despite intensive efforts by many investigators, the molecular basis of PCOS remains unclear

What is PCOS is a complex trait modulated by what genetic factors?

• Intrauterine and environmental exposures

• Insulin resistance

• Pancreatic β cell function

• Steroidogenesis

• Steroid hormone metabolism

What are the criteria for PCOS?

• Oligomenorrhea: Infrequent periods

• Hyperandrogenism

• Polycystic ovaries on Ultrasound

What is a cyst?

• The definition of a cyst is a fluid-filled sac

• Cysts can occur anywhere in the body

Why do we people develop cyst?

• Individuals can develop "cysts" due to eggs not being released over time

• The follicles keep growing and form multiple "cysts"

Explain the difference between normal ovary and PCOS?

What are the gross characteristics of the polycystic ovaries?

1. Bilateral enlarged ovaries with a smooth and thickened capsule

2. On cut section, multiple follicular cysts surrounded by abundant ovarian stroma are found throughout the cortex of the ovary

What are the microscopic characteristics of PCOS?

• Subcapsular antral follicles arrested at mid-stage of development

• Hyperplasia of theca cell layer

What is the description of how theca and granulosa cells appear in pcos

• PCOS follicle has thickened theca cell layer with disrupted and degenerative granulosa cells

• Greater width in theca cells, less of a width in granulosa cell layers.

What is hirsutism?

• Excessive hair growth

• The degree of which is variable from mild to severe

What is the most distinct and visible clinical feature of PCOS?

• The most distinctive and visible clinical feature of PCOS is hirsutism

What is the pathophysiology of hirsutism?

• In PCOS, the amount of hirsutism has been correlated to serum androgen concentrations

• Free Testosterone increased when Sex Hormone Binding Globulin decreases

How can pre-existing conditions affect hirsutism?

• Coexisting conditions that alter the bioactivity of androgens, such as hypothyroidism and obesity may also give rise to excessive hair growt

What is menstruation dysfunction?

• Menstrual dysfunction is primarily characterized by irregular, infrequent, or absent menstrual bleeding

• In approximately 20% of people, there is complete absence of menses, whereas 5% to 10% of cases demonstrate regular ovulatory function

When can the onset of chronic anovulation emerges?

• In some, the onset of chronic anovulation emerges beyond adolescence, but this is unusual

Does recognition of normal ovulation in PCOS?

Is significant in that a history of regular menstrual cycles does not exclude the diagnosis

What change in ovulation may occur in women with PCOS later in reproductive life?

It has been reported that in late reproductive life, PCOS women begin to experience regular ovulation [for unknown reasons]

What are some characteristics aging PCOS women with regular menstrual cycles appear to have?

[1] smaller follicle cohort,

[2] higher serum FSH levels and,

[3]  lower androgen levels compared to age-matched PCOS with persistent anovulation

What is the ovarian morphology?

• Classically, those with PCOS have enlarged ovaries with numerous peripheral small antral follicles and increased central stroma

• Normal follicular growth appears to occur up to the mid-antral stage, after which maturation ceases

What happens to the granulosa reaches the mid-antral stage?

The granulosa cell layer becomes progressively degenerative and the entire structure may have the appearance of a thin-walled cyst

What happens to the theca reaches the mid-antral stage?

Layer that surrounds the follicle becomes substantially hyperplastic and thickened compared to that of normal follicles and is responsible for increased androgen production

What do histomorphometric studies show?

Revealed a twofold to threefold increase in the numbers of primary, secondary, and tertiary follicles compared to those of the normal ovary

What do histomorphometric studies show in ?

• Ovaries are endowed with a greater number of follicles

• Whether the rate of programmed cell death is decelerated compared to the normal ovary has not been systematically studied