Endocrine Disorders Affecting Reproduction Flashcards
What are the key hormones in the reproductive pathway?
Follicle stimulating hormone (FSH) stimulates follicles to grow and produce oestrogen. Leutinising hormone (LH) acts on thecal cells primarily which produce androgens, leading to ovulation
In what manner is GnRH released?
GnRH is released in a pulsatile manner, causing pulsatile LH release.
What happens if you give continuous GnRH?
Continuous GnRH will eventually suppress LH and FSH. This is used in IVF to control the cycle and growth of multiple follicles without the risk of spontaneous ovulation.
What can go wrong with the hypothalamo-pituitary-gonadal axis?
- Central pathology: Lack of secretion of LH and FSH due to hypothalamic/pituitary disease. 2. Gonadal damage: Failure of germ cell production and lack of sex steroid production. 3. Polycystic ovary syndrome: Normal hormone levels but not ovulating.
How do HPG axis issues present in females?
Menstrual history is important: Oligoamenorrhoea, Amenorrhoea, Infertility, Oestrogen deficiency symptoms, Hirsutism, acne, androgenic alopecia, Weight gain/loss, Galactorrhoea.
What are the causes of amenorrhoea?
Pregnancy, central causes (hypothalamic, pituitary), ovarian causes (Turner’s syndrome, premature ovarian failure), polycystic ovary syndrome, and miscellaneous causes (thyrotoxicosis, chronic disease).
What is hypothalamic amenorrhoea?
It is caused by severe marked weight loss, exercise, or bulimia, leading to pituitary gland dysfunction.
What is congenital leptin deficiency?
Leptin deficiency affects food intake and reproductive system functioning, leading to severe obesity, hyperphagia, and hypogonadotropic hypogonadism.
What are the main anterior pituitary hormones?
ACTH (adrenal cortex regulation), TSH (thyroid hormone regulation), GH (growth), LH/FSH (reproductive control), PRL (prolactin for breast milk production).
How is PRL secretion controlled?
PRL is synthesized in lactotrophs and is regulated by dopamine, which inhibits its release. Disruption of dopamine can lead to lactation.
What causes physiological hyperprolactinaemia?
Stress results in excess PRL release, which is more common in women and rarely exceeds 850-1000 mU/L.
What are the clinical features of hyperprolactinaemia?
In premenopausal women: hypogonadism, oligomenorrhoea, galactorrhoea. In postmenopausal women: usually none due to existing amenorrhoea.
What are the causes of pathological hyperprolactinaemia?
PRL-secreting pituitary tumours (prolactinomas), loss of inhibitory effect from hypothalamus-derived dopamine, drugs (DA antagonists), and hypothyroidism.
What does premature ovarian insufficiency usually present with?
Amenorrhoea, oestrogen deficiency, and elevated LH/FSH levels (>30 IU/L) in women under 45.
What are the causes of premature ovarian insufficiency?
Congenital causes (Turner’s syndrome), autoimmune conditions, iatrogenic causes (chemotherapy, surgery), and genetic mutations.
What are the phenotypes of Turner’s syndrome?
Short stature, low hairline, widely spaced nipples, webbed neck, nevi, small fingernails.
How do autoimmune conditions lead to POI?
POI can be caused by autoimmune diseases such as Graves Disease, Addison’s, and diabetes, with 2-10% of cases linked to adrenal autoimmunity.
What is the mechanism of autoimmune POI?
Inflammatory infiltration of follicles and production of anti-ovarian antibodies lead to apoptosis and atrophy.
What is the link between Fragile X premutation and POI?
1/200 females have the genetic change leading to FXPOI, which accounts for about 4-6% of all POI cases. It is inherited in an X-linked dominant pattern.
What is the management of POI?
Diagnosis on serial FSH and E2 levels, karyotyping, screening for autoimmune diseases, and managing with oestrogen replacement.
What is Polycystic Ovary Syndrome (PCOS)?
The most common endocrine condition affecting 10% of pre-menopausal women, with an unknown aetiology possibly related to insulin sensitivity.
What is PCOS associated with?
Oligoamenorrhoea, hirsutism, obesity, infertility, polycystic ovaries on ultrasound, and hyperandrogenism.
What happens if you do not protect the endometrium from oestrogen exposure?
You get endometrial hyperplasia due to unopposed oestrogen exposure.
What is the Rotterdam diagnostic criteria for PCOS?
2 out of 3: Oligo-/Amenorrhea, clinical or biochemical signs of hyperandrogenaemia, polycystic ovaries.
What are the clinical features of PCOS?
PCO, acanthosis nigricans, insulin resistance, obesity, androgen excess, and anovulation.
What is hirsutism?
Male hormone dependent hair growth in areas such as the upper lip, chin, and abdomen.
What is Hirsutism?
Male hormone dependent hair growth.
How is Hirsutism categorised?
Upper lip, chin, anterior neck, sideburn, breasts, pubic hair. A score >8 on the score of hirsutism indicates hirsutism.
What is androgenic alopecia?
Male-pattern baldness that can also occur in females.
What clinical problems arise with pregnant women with PCOS?
Oligo-/Amenorrhea & Infertility are the most common clinical problems. Risk of gestational diabetes and pregnancy-related hypertension is ten times increased due to insulin resistance.
What is the IVF risk for pregnant women with PCOS?
Increased risk of Ovarian Hyperstimulation Syndrome (OHSS). Avoided by using an antagonist IVF protocol with a GnRH trigger injection for egg maturation.
What risks can OHSS cause in a pregnant woman with PCOS?
Can cause fluid leaking into the 3rd space, dehydration, ascites, kidney problems, and high risk of venous thromboembolism.
What can be treated in PCOS?
Obesity and Oligo/Amenorrhea can be treated with Metformin, lifestyle modification, and MPA (progesterone).
What are the three types of anti-androgenic oral contraceptives?
Dianette, which is not recommended anymore due to increased risk of venous thromboembolism, and two others with specific anti-androgen progesterone.
What is 21-hydroxylase deficiency?
Causes congenital adrenal hyperplasia and can mimic PCOS.
What are the two forms of 21-hydroxylase deficiency?
Classical form (neonatal/infancy presentation) and Non-classical form (childhood/adult presentation).
How do you test for 21-hydroxylase deficiency?
If 17 OHP is high, it indicates 21-hydroxylase deficiency.
What is androgen insensitivity syndrome?
A spectrum of disorders due to mutations in the Androgen receptor, including Complete, Incomplete, and Reifensteins.
What are the features of someone with androgen insensitivity syndrome?
Female external genitalia, short blind-ending vagina, no uterus, absent prostate, and gynaecomastia.
What is 5a-reductase deficiency?
A condition where individuals appear female but are genetically male (46XY) and unable to convert Testosterone to DHT.
How does hypogonadism present in males?
Delayed puberty, psychological effects, gynaecomastia, loss of body hair, decreased muscle mass, and infertility.
What are the causes of hypogonadism I in males?
Primary gonadal failure due to trauma, chemotherapy, infections, and chromosomal abnormalities.
What are the causes of hypogonadism II in males?
Secondary gonadal failure due to pituitary tumors, hyperprolactinaemia, and hypothalamic disorders.
How is hypogonadism investigated?
Clinical examination, LH, FSH, Testosterone levels, and further investigations based on results.
What is Klinefelter’s syndrome?
Affects 1:1000 males with a 47 XXY karyotype, leading to primary hypogonadism and feminisation.
What is myotonic dystrophy?
An autosomal dominant condition that can cause progressive muscular weakness, myotonia, and primary gonadal failure.
What is Kallman’s syndrome?
Idiopathic hypogonadotropic hypogonadism with anosmia in 75% of cases.
How can testosterone be replaced?
Through tablets, buccal mucosa, injections, transdermal patches, or subdermal implants.
What is androgen abuse?
The use of designer drugs that increase testosterone, leading to various health hazards.
What are the causes of male infertility?
Endocrine causes are rare; assessment includes history, examination, and seminal fluid analysis.
