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Reproductive Endocrinology Flashcards

1
Q

What are primordial germ cells?

A

earliest recognisable germ cells

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2
Q

What is oogonia?

A

Structure formed after the completion of the last pre-meiotic division before they become oocytes

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3
Q

Secondary oocytes have gone through how many meiosis cycles?

A

2

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4
Q

When is the first polar body formed in female germ cells?

A

One of the 2 products of the first stage of meiosis

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5
Q

How is the 2nd polar body formed?

A

When sperm enters the oocyte and the 2nd meiotic division is complete

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6
Q

What are the 2 phases of the ovarian cycle?

A

Follicular

Luteal

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7
Q

What happens in the follicular phase of the ovarian cycle?

A

Maturation of egg until it’s ready for ovulation at midcycle

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8
Q

What happens in the luteal phase of the ovarian cycle?

A

Development of the luteum

Induces preparation of the reproductive tract for pregnancy (if fertilisation occurs)

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9
Q

What are the primary follicles?

A

A layer of granulosa cells which surrounds the primary oocyte before birth

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10
Q

How many primary follicles are present in a female when she is born?

A

~2 million

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11
Q

Does the number of primary follicles in a females ovaries increase or decrease as she gets older?

A

Decrease

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12
Q

How is the secondary follicle formed?

A

The oocyte grows around 1000x its size and the follicle expands and becoems differentiated under the influence of hormones

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13
Q

How many eggs will be ovulated within a woman’s lifetime?

A

~400

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14
Q

What happens to the follicular cells after ovulation?

A

They undergo luteinisation to transform into the corpus luteum

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15
Q

What hormone does the corpus luteum secrete?

A

Progesterone

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16
Q

What hormone is secreted in the follicular phase?

A

Oestrogen

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17
Q

After ovulation for how long does the corpus luteum grow before reaching its maximum size?

A

8-9days

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18
Q

If the egg has not become fertilized then what will happen to the corpus luteum?

A

Lasts for ~14 days post-ovulation and then degenerates signalling a new ovarian cycle

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19
Q

If the egg DOES become fertilized then what happens to the corpus luteum?

A

It persists in teh ovary and produces progesterone and oestrogen in increasing amounts until after pregnancy

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20
Q

The hypothalamus secretes GnRH which acts next on which part of the body?

A

Anterior pituitary gland

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21
Q

Once acted upon by GnRH, what does the anterior pituitary release?

A

FSH

LH

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22
Q

What does FSH do in the ovarian cycle?

A

Acts on the ovary to stimulate follicle development

FSH and LH stimulate oestrodiol secretion and ovulation

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23
Q

What is the role of LH in the ovarian cycle?

A

Acts on the ovary to stimulate follicle maturation, ovulation and development of the corpus luteum

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24
Q

What do FSH and a little LH cause to happen in the ovary in the follicular phase?

A

Upto 15 follicles begin to mature i.e. their granulosa and theca cells develop

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25
What do the theca cells cause to happen in the follicular phase?
Produce androgen which is converted by the granulosa to oestradiol which thickens the endometrium and thins the cervical mucous
26
What does the dominant follicle possess so that it can continue along the cycle?
LH receptor
27
At mid cycle, high levels of oestrogen are produced, the hypothalamus does what in response to this?
Release GnRH thus FSH and LH are released in a surge from the ant. pituitary
28
What happens to the FSH and LH levels during ovulation?
They begin to fall
29
after ovulation what happens to the remaining granulosa cells from the dominant follicle?
Proliferate to form the corpus luteum and secrete progesterone
30
What does hCG stand for?
Human chorionic gonadotrophin
31
What happens to the corpus luteum if it does not detect hCG after 12 days post-ovulation?
It degenerates and becomes the corpus albicans
32
When the corpus luteum becomes the corpus albicans progesterone and oestrogen levels fall, what can now happen?
A new cycle can recommence
33
If the corpus luteum does detect levels of hCG then what will it do?
Produces progesterone until ~6weeks into the pregnancy when the placenta takes over this role.
34
What hormones stimulate spermatogenesis?
FSH | Testosterone
35
What decreases FSH secretion in men?
Inhibin
36
What is the name of the cells which secrete androgen-binding globulin (ABG) and inhibin, and where are they found?
Sertoli cells in the seminiferous tubules
37
LH stimulates secretion of what other hormone?
Testosterone
38
What effect does testosterone have on the secretion of GnRH?
It decreases the rate of secretion
39
Testosterone goes on to form dihydrotestosterone, what does this do?
enlarges the male sex organs given males their secondary sexual characteristics anabolism
40
What is oligomenorrhoea?
A decrease in the frequency of periods to <9/year
41
What is primary amenorrhoea?
Failure of menarche by 16
42
What is secondary amenorrhoea?
Cessation of periods in an individual for >6months in an individual who has previously menstruated
43
What are the physiological causes of amennorhoea?
Pregnancy | Post-menopausal
44
What can cause primary amenorrhoea?
Congenital problems (Turner's syndrome, Kallman's syndrome)
45
What can cause secondary amenorrhoea?
Ovarian problems - PCOS, POF Uterine adhesions Hypothalamic dysfunction Pituitary problems
46
What are the symptoms of oestrogen deficiency?
Flushing Libido decreased Dysparenuria
47
What are the features of PCOS/androgen excess?
Hirsutism | Acne
48
What is one of the main symptoms of hypopituitarism or a pituitary tumour?
Galactorrhoea
49
What investigations should be done in ALL woman presenting with amenorrhoea?
LH, FSH, Oestradiol | TFTs and prolactin
50
How is female hypogonadism identified?
Low levels of oestrogen
51
What are the signs/symptoms associated with primary hypogonadism?
Problem with the ovaries High LH/FSH - hypergonadotrophic hypogonadism e.g. POF
52
What are the signs/symptoms associated with secondary hypogonadism?
Problem with the hypothalamus or pituitary Low FSH/LH - hypogonadotrophic hypogonadism Low oestradiol
53
What happens in premature ovarian failure (POF)?
Amenorrhoea, low oestrogen and high gonadotrophins in women <40y/o as a result of loss of ovarian function
54
How is POF diagnosed?
FSH >40 on 2 separate occasions >1month apart
55
What can cause POF?
Chromosomal abnormalities Gene mutations AI disease Iatrogenic (radio/chemo)
56
What are the symptoms of functional hypothalamic amenorrhoea?
Weight change Stress Exercise (too much) Eating disorders
57
What are the causes of functional hypothalamic amenorrhoea?
``` Anabolic steroids Systemic illness Iatrogenic Recreational drugs Head trauma Infiltrative disorders ```
58
What happens within the body during functional hypothalamic amenorrhoea?
Abnormal hypothalamic GnRH secretion leading to decreased gonadotrophin pulsations This leads to low LH and FSH and thus low oestradiol
59
What is Kallman's syndrome?
A genetic disorder causing a loss of GnRH secretion +/- anosmia
60
Does Kallman's syndrome affect males or females more?
Males (x4)
61
Why is anosmia found in 75% of Kallman's syndrome sufferers?
There are no olfactory bulbs present
62
What pituitary disorders can lead to loss of LH/FSH stimulation?
Presence of a non-functioning pituitary macroadenoma (pressure mass effects lead to hypopituitarism) Empty sella Pituitary infarction
63
What pituitary disorders can lead to hyperprolactinaemia?
Presence of a micro- or macro-prolactinoma | Some drugs e.g. dopamine agonists
64
Other than hyperprolactinaemia and a loss of LH/FSH stimulation, what other signs can indicate a pituitary disorder?
low FSH/LH | Low oestradiol
65
What are the ovarian causes of amenorrhoea?
PCOS Ovarian failure - high gonadotrophins Congenital problem with ovarian development
66
What are the Rotterdam criteria, of which 2/3 must be present for a diagnosis of PCOS to be given?
Menstrual irregularity Hyperandrogenism (hirsutism and high free testosterone) Polycystic ovaries
67
What congenital problems of the ovaries can lead to amenorrhoea?
``` Absence of uterus Vaginal atresia (absence of normal opening) Turner's syndrome Testicular feminisation Congenital adrenal hyperplasia ```
68
What can a genetic predisposition to excess ovarian androgen secretion cause?
Polycystic ovaries
69
What can cause increased testosterone in a female?
Polycystic ovaries Pituitary gland overproduction Insulin resistance and hyperinsulinaemia
70
What can excess testosterone do in a female?
Increases LH Causes insulin resistance and hyperinsulinaemia Hirsutism
71
What is hirsutism?
Excess hair when referring to women with male pattern hair distribution
72
What causes hirsutism?
Androgen excess at the hair follicle
73
What conditions can cause hirsutism?
PCOS Familial Idiopathic CAH All of the above have long histories with not dramatically high testosterone levels and no signs of virilisation. All those below have a short history and deepening of voice and clitoromegaly Adrenal or ovarian tumours
74
What is CAH?
An inherited group of disorders characterised by a deficiency in one of the enzymes necessary for cortisol synthesis.
75
What is 90% of CAH caused by?
21-alpha-hydroxylase deficiency causing excess testosterone | Autosomal recessive disorder with a varied clinical presentation
76
When is classic CAH diagnosed?
Diagnosed in infancy with virilisation and salt-wasting
77
When is non-classic (partial) CAH diagnosed?
In adolesence/ early adulthood with hirsutism, menstrual disturbance, infertility due to anovulation
78
What are androgen secreting tumours associated with?
Rapid onset of symptoms Signs of virilisation Increased testosterone MRI showing adrenal and ovarian tumours >1cm diameter.
79
If hirsutism is caused by PCOS then how is it treated?
Oral contraceptive pill Anti-androgens (local and general) Cosmesis
80
If hirsutism is caused by late onset CAH, then what is it treated by?
low dose glucocoticoid to suppress ACTH drive
81
What is different about the genetic makeup of an individual with Turner's syndrome?
A female with only 1 X chromosome
82
How common is Turner's syndrome?
1 in 2000 live births
83
How does Turner's syndrome present in paediatrics?
Short stature | Failure to progress through puberty
84
How does Turner's syndrome present in adults?
Primary or secondary amenorrhoea | Infertility
85
What other signs or symptoms can affect the CVS in Turner's syndrome?
Coarctication of the aorta Bicuspid aortic valve Hypoplastic left heart
86
What other signs or symptoms can affect the GI system in Turner's syndrome?
GI bleeds | Increased incidence of Crohns and UC
87
What other signs or symptoms can affect the body in Turner's syndrome?
``` Lymphoedema Hypothyroidism Osteoporosis Scoliosis 1/3 have renal abnormalities Otitis media ```
88
What is XX gonadal dysgenesis?
Absent ovaries but no chromosomal abnormality
89
What is testicular feministaion?
Androgen insensitivity syndrome | Genetically XY male (with testes) but in the complete form, phenotypically female
90
How long does a normal menstrual cycle last?
28-35 days
91
How long do oligomenorrhoea cycles last for?
>35 days
92
The surge of what hormone triggers ovulation?
LH
93
What hormone peaks before ovulation?
Oestrodiol
94
What hormone peaks after ovulation?
Progesterone
95
How can ovulation be confirmed in an individual with regular cycles?
Midluteal (day21) serum progesterone (>30nmol/L) x 2 samples Basal body temperature changes Cervical mucous changes
96
If a cycle lasts longer than 28 days, which phase of the cycle is likely to be the one which lasts longer?
Follicular
97
How can you confirm ovulation in an individual with irregular cycles?
``` Midluteal progesterone (day 21) Early follicular phase (day 2-5) - Serum FSH/LH, oestradiol - Serum prolactin, TSH - Free androgen index Progesterone challenge test ```
98
What is the progesterone challenge test?
If a patient bleeds a week-10days after a 5 day course of progesterone then this indicates normal oestrogen levels
99
What radiological investigations can be done to assess ovulation?
Transvaginal USS ovaries to look for ovarian morphology and serial scans to look for follicular growth and ovulation If required: MRI pituitary fossa Bone density scan
100
What is hypothalamic pituitary failure?
Where the hypothalamus does not release adequate GnRH.
101
What are the effects of hypothalamic pituitary failure?
Hypogonadotrophic hypogonadism Oestrogen deficiency Normal proclatin Amenorrhoea
102
What can cause hypothalamic pituitary failure?
``` Stress Exercise Anorexia Brain/Pituitary tumours Head Trauma Kallman's syndrome Drugs (steroids/Opiates) ```
103
How is hypothalamic pituitary failure managed?
Stabilise weight - BMI >19 Give pulsatile GnRH every 90 mins SC or IV (pump worn continuously) Gonadotrophin daily injections Need to monitor response with USS
104
How does hypothalamic pituitary dysfunction manifest itself?
Normal gonadotrophins and oestrogen levels Anovulation PCOS
105
How often is insulin resistance seen in individuals with PCOS?
50-80% of patients
106
Why does compensatory hyperinsulinaemia occur in individuals with insulin resistance due to PCOS?
There is a normal pancreatic insulin reserve
107
What do 20% of patients with PCOS and insulin resistance also have?
Frank glucose intolerance and Non-insulin requiring DM
108
Insulin increases sex hormone binding globulin, what does this do to free testosterone levels?
Increases them and leads to hyperandrogenism
109
Before any treatment is given for anovulation associated with PCOS, what management should be implemented?
``` Weight loss Stop smoking + drinking alcohol Go on Folic acid 400mcg/5mg daily Check rubella immunity Check partners semen analysis Check fallopian tube is patent ```
110
What is the 1st line treatment for induction of ovulation in a woman with PCOS?
Clomifene citrate - an anti-oestrogen 50-100mg tab given on days 2-6 of the ovarian cycle Only prescribable for 6-9months
111
Other than Clomifene citrate, what other treatments exist for ovulation induction in individuals with PCOS?
Gonadotrophin therapy Laproscopic ovarian diathermy Metformin - with lifestyle modification (reduces androgen production)
112
What are the features of ovarian failure?
Increased gonadotrophins | Decreased Oestrogen
113
What are the causes of ovarian failure?
Premature - Turner syndrome, XX gonadal agenesis, premature menopause AI ovarian failure Pelvic radio/chemo
114
What are the signs and symptoms of premature ovarian failure?
Menopause 30IU/L | Low oestradiol
115
How is premature ovarian failure treated?
HRT - hormone replacement therapy Egg or embryo donation Ovary/egg/embryo cryo-preservation prior to potentially POF causing treatments Counselling/ support network
116
What questions should be asked in a history of somebody being investigated for hyperprolactinaemia?
Amenorrhoea? Galactorrhoea? Current medications?
117
What examination is it important to do when investigating hyperprolactinaemia and why?
Visual fields - Invading tumour on optic chiasm
118
What investigations should be done when investigating hyperprolactinaemia?
``` FSH/LH (normal) Oestrogen (low) Serum prolactin (high) TFTs (normal) MRI to diagnose micro/macro prolactinoma ```
119
How is hyperprolactinaemia treated?
Dopamine agonists - Cabergoline - longer acting - Bromocriptine - conventional Should be stopped when pregnancy occurs
120
What are the risks of ovulation induction and ART?
Ovarian hyperstimulation Multiple pregnancy Potential risk of ovarian cancer if used for >12 months
121
How common is infertility?
Affects 1 in 6 couples
122
How is infertility defined?
Failure to achieve a clinical pregnancy after >12 months of regular unprotected sexual intercourse - in absence of any known reason
123
What is primary infertility?
Infertility in a couple who have never concieved a child
124
What is secondary infertility?
Infertility is a couple who have previously concieved (pregnancy may not have been successful)
125
What factors increase the chance of a successful pregnancy?
Woman <2 cups coffee daily | No recreational drugs
126
What factors decrease the chance of a successful pregnancy?
``` Woman >35 No previous pregnancy >3 years trying Intercourse mistimed Woman's BMI 30 1 or both partners smoke Caffeine intake = > 2 cups of coffee/day Regular recreational drugs Excess alcohol in either partner ```
127
What disorders other than those involved in the gynecological system can cause infertility?
CKD testosterone secreting tumours CAH Drugs: depo-provera, explanom, OCP
128
What are the infective causes of tubal disease in women?
Pelvic inflammatory disease (STIs etc.) Transperitoneal spread of appendicitis or an intra-abdominal abscess Following invasive procedures or surgery of that area
129
What are the non-infective causes of tubal disease?
``` Endometriosis Surgical (sterilisation, ectopic pregnancy) Fibroids Polyps Congenital ```
130
What are the clinical features of tubal disease in women?
``` Abdo pain Febrile Cervical excitation Dysmenorrhoea Ectopic pregnancy Vaginal discharge Dyspareunia Menorrhagia Infertility ```
131
What is the prevalence of endometriosis?
approx 20%
132
What is endometriosis?
Presence of endometrial glands outside the uterine cavity
133
What are the clinical features of endometriosis?
``` Dysmenorrhoea Dysparenuia menorrhagia painful defecation chronic pelvic pain 'chocolate' cysts on ovary ```
134
What is a varicocele?
Varicose veins next to the testis (abnormal enlargement of pampiniform venous plexus in the scrotum)
135
What are the non-obstructive causes of male infertility?
Genetic - Klienfelters syndrome Chemo/radio undescended testes idiopathic
136
What clinical features can arise from non-obstructive male infertility?
``` decreased testicular volume decreased secondary sexual characteristics Vas deferens present high LH/FSH Low testosterone ```
137
What are the obstructive causes of male infertility?
Congenital absence (CF) Infection Vasectomy
138
What clinical features are typical of obstructive male infertility?
Normal testicular volume Secondary sexual characteristics Vas deferens may be absent Normal FSH, LH and testosterone
139
What endocrine disorders can cause male infertility?
``` Acromegaly Cushings Disease Hyperprolactinaemia Anorexia Hyper or hypothyroidism ```
140
What are the causes of erectile difficulties?
Diabetes Spinal cord injury Psychosexual
141
What disorders can affect the sperm?
Rare defects e.g. globospermia, Kortagne's syndrome
142
When investigating infertility what examinations should be done of the female?
BMI Body hair distribution and galactorrhoea Pelvic exam - uterine and ovarian abnormalities/tenderness/mobility
143
When investigating infertility what examinations should be done of the Male?
BMI | Gential exam - size/position of testes, penile abnormalities, presence of vas deferens, presence of varicoceles
144
What investigations should be performed for an infertile woman?
Endocervical swab for chlamydia Cervical smear if due Blood for rubella immunity Midluteal progesterione
145
What are 2 tests for tubal patency?
hysterosalpingiogram | Laparoscopy
146
What are the risk factors for a hysterosalpingiogram?
Tubal/pelvic pathology
147
When is laparoscopy indicated?
In possible tubal/pelvic disease
148
When is laparoscopy contraindicated?
Obesity Previous pelvic surgery Crohns
149
When would a hysteroscopy be necessary for testing tubal patency?
Suspected or known pathology e.g. uterine septum, adhesions, polyps
150
When would a pelvic ultrasound be indicated in testing for tubal patency?
When an abnormality is found on pelvic exam
151
When would an endocrine profile and chromosomal analysis be necessary for testing of tubal patency?
Anovulatory or infrequent periods Hirsute Amenorrhoea
152
What measurements should be taken when performing a semen analysis?
``` Volume pH Concentration Motility Morphology WBC ```
153
If semen analysis is abnormal what other tests should be done when investigating the infertile male?
LH/FSH Testosterone Prolactin TFTs
154
If semen analysis is severely abnormal/azoospermic then what tests should be performed in the infertile male?
Endocrine profile Chromosome analysis Screen for CF (associated with absent vas deferens) Testicular biopsy
155
If an abnormality is found on a genital exam of a male then what test should be done next?
Scrotal USS
156
What are the first line agents used in ovulation induction?
Antioestrogens - Clomifene citrate + tamoxifen | Aromatase inhibitors - Letrozole/Anastrozole (not in UK)
157
What are the 2nd line agents for ovulation induction?
Clomifene citrate + metformin Gonadotrophin therapy - daily injections Laproscopic ovarian diathermy (drilling)
158
How is male infertility treated?
Surgery for obstructed vas deferens Intrauterine insemination in mild disease Intracytoplamic sperm injection into egg (ICSI) ICSI combined with surgical sperm aspiration from epididymis or testicle Donor insemination

x 2nd Year Medicine (10 decks)

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