Polycystic ovary syndrome (PCOS)
• Most common endocrine and metabolic syndrome in women of reproductive age
• Depending on geographical location, 6-20% of reproductive age women affected
• Cause unknown – but genetic, environmental and lifestyle factors involved
• Symptoms depend on age/stage of life
o Adolescents – irregular periods
o Hirsutism – excessive body hair
o Acne
o Insulin resistance
o Fast weight gain/difficult to lose weight (due to insulin resistance)
o Male pattern baldness
o Infertility (but can still conceive with PCOS)
o Women may not know they have PCOS until trying to conceive and can’t
• Diagnosis – Rotterdam (2004) criteria; any 2 of the following
▪ Irregular periods (cycle <21 days or >35 days)
▪ Hyperandrogenism
▪ Clinical signs – hirsutism, acne
▪ Biochemical test – blood test for free testosterone, sex-binding hormone
gonadotrophin (SBHG) or a ratio of both
• Morphology
o > 12 follicles on ovary
o ‘cysts’ are follicles
o Not diagnosed on morphology alone as common for women to have lots of follicles of
ovaries
• Pathophysiology
o Main drivers of PCOS (direction of causality unknown)
▪ Insulin resistance
▪ Hyperandrogenism
▪ Inflammation
• No cure – must be managed through lifestyle, diet, birth control, diabetic dug metformin, regular
sleep and exercise
• Infertility stems from unpredictable ovulation
• If diagnosed and managed from young age, reduces long-term metabolic and reproductive
complications
• Low carbohydrate diet to combat insulin resistance
• Vitamin D
o Deficiency seen in 65-87% of PCOS cases
o VitD receptors in ovaries and endometrium suggest role in female reproduction
o Deficiency associated with
▪ Dysregulation of FSH, LH, testosterone
, ▪ Impaired ovulatory function
▪ Dysregulated follicular development
▪ Oxidative stress
o Sequestered in adipose tissue during PCOS weight gain (due to insulin resistance)
o Study found VitD supplement improved follicular development
• Inositol
o Sugar alcohol found in fruit, grains, beans, and nuts
o Produced in body from glucose or taken as supplement
o 2 most common forms function as insulin 2nd messengers and mediate different actions of
insulin
▪ Myo-inositol (M1) converts to inositolphosphoglycan (IPG) 2nd messenger MI-IPG
involved in cellular glucose uptake
▪ D-chiro-inositol (DCI) converts to IPG 2nd messenger DCI-IPG involved in glycogen
synthesis
o In PCOS, deficiency of IPGs in tissues or altered metabolism of inositol to IPG mediators
could play role in insulin resistance
o Nestler et al (1999) – DCI supplement
▪ Significant increase in proportion of women who ovulated
▪ Significant decrease in free testosterone
▪ Significant decrease in plasma triglycerides
Haemolytic disease of the foetus and newborn
• Human blood groups
o Blood group antigens cause blood group incompatibility
o Most important during transfusions and incompatible pregnancies
o Blood antigens are expressed as membrane proteins (e.g., Rh) or as glycoproteins that are
attached to membrane proteins/lipids (e.g., ABO)
o ABO is a carbohydrate system - An enzyme synthesises and adds different antigens to
different glycoproteins/lipids
o Rh proteins are transmembranous with the antigen expressed on an external loop
o There are 43 different blood groups systems – each confer a wide range of functions to red
blood cells
▪ Complement control
▪ Structural
▪ Carbohydrates (ABO)
▪ Transport (Rh)
▪ Surface enzyme
▪ Cytokine receptor
▪ Cell adhesion
o Only ABO and Rh are routinely tested for
• Rh blood group system
o First described by Landsteiner in 1940
o 2nd most significant after ABO group
o Major cause of HDFN
o RhD gene on chromosome 1
▪ 10 exons
▪ Rhesus boxes either side of gene
▪ Smp1 gene after (in between RhD and RhCE genes)
▪ RhD and RhCE genes are ‘tail-to-tail’ – 1 → 10; 10 → 1
▪ Arose as duplication from ancestral RhCE gene
o RhD positive = RhD antigens on erythrocytes
o RhD negative (Caucasian) = missing entire RhD gene
• Most common endocrine and metabolic syndrome in women of reproductive age
• Depending on geographical location, 6-20% of reproductive age women affected
• Cause unknown – but genetic, environmental and lifestyle factors involved
• Symptoms depend on age/stage of life
o Adolescents – irregular periods
o Hirsutism – excessive body hair
o Acne
o Insulin resistance
o Fast weight gain/difficult to lose weight (due to insulin resistance)
o Male pattern baldness
o Infertility (but can still conceive with PCOS)
o Women may not know they have PCOS until trying to conceive and can’t
• Diagnosis – Rotterdam (2004) criteria; any 2 of the following
▪ Irregular periods (cycle <21 days or >35 days)
▪ Hyperandrogenism
▪ Clinical signs – hirsutism, acne
▪ Biochemical test – blood test for free testosterone, sex-binding hormone
gonadotrophin (SBHG) or a ratio of both
• Morphology
o > 12 follicles on ovary
o ‘cysts’ are follicles
o Not diagnosed on morphology alone as common for women to have lots of follicles of
ovaries
• Pathophysiology
o Main drivers of PCOS (direction of causality unknown)
▪ Insulin resistance
▪ Hyperandrogenism
▪ Inflammation
• No cure – must be managed through lifestyle, diet, birth control, diabetic dug metformin, regular
sleep and exercise
• Infertility stems from unpredictable ovulation
• If diagnosed and managed from young age, reduces long-term metabolic and reproductive
complications
• Low carbohydrate diet to combat insulin resistance
• Vitamin D
o Deficiency seen in 65-87% of PCOS cases
o VitD receptors in ovaries and endometrium suggest role in female reproduction
o Deficiency associated with
▪ Dysregulation of FSH, LH, testosterone
, ▪ Impaired ovulatory function
▪ Dysregulated follicular development
▪ Oxidative stress
o Sequestered in adipose tissue during PCOS weight gain (due to insulin resistance)
o Study found VitD supplement improved follicular development
• Inositol
o Sugar alcohol found in fruit, grains, beans, and nuts
o Produced in body from glucose or taken as supplement
o 2 most common forms function as insulin 2nd messengers and mediate different actions of
insulin
▪ Myo-inositol (M1) converts to inositolphosphoglycan (IPG) 2nd messenger MI-IPG
involved in cellular glucose uptake
▪ D-chiro-inositol (DCI) converts to IPG 2nd messenger DCI-IPG involved in glycogen
synthesis
o In PCOS, deficiency of IPGs in tissues or altered metabolism of inositol to IPG mediators
could play role in insulin resistance
o Nestler et al (1999) – DCI supplement
▪ Significant increase in proportion of women who ovulated
▪ Significant decrease in free testosterone
▪ Significant decrease in plasma triglycerides
Haemolytic disease of the foetus and newborn
• Human blood groups
o Blood group antigens cause blood group incompatibility
o Most important during transfusions and incompatible pregnancies
o Blood antigens are expressed as membrane proteins (e.g., Rh) or as glycoproteins that are
attached to membrane proteins/lipids (e.g., ABO)
o ABO is a carbohydrate system - An enzyme synthesises and adds different antigens to
different glycoproteins/lipids
o Rh proteins are transmembranous with the antigen expressed on an external loop
o There are 43 different blood groups systems – each confer a wide range of functions to red
blood cells
▪ Complement control
▪ Structural
▪ Carbohydrates (ABO)
▪ Transport (Rh)
▪ Surface enzyme
▪ Cytokine receptor
▪ Cell adhesion
o Only ABO and Rh are routinely tested for
• Rh blood group system
o First described by Landsteiner in 1940
o 2nd most significant after ABO group
o Major cause of HDFN
o RhD gene on chromosome 1
▪ 10 exons
▪ Rhesus boxes either side of gene
▪ Smp1 gene after (in between RhD and RhCE genes)
▪ RhD and RhCE genes are ‘tail-to-tail’ – 1 → 10; 10 → 1
▪ Arose as duplication from ancestral RhCE gene
o RhD positive = RhD antigens on erythrocytes
o RhD negative (Caucasian) = missing entire RhD gene
