The Reproductive System Flashcards

1
Q

What are the two functions of the testes? Which hormones influence which cells?

A

In the male, the testis subserves two principal functions:

1) Synthesis of testosterone by the interstitial Leydig cells under the control of lutenising hormone (LH); and
2) Spermatogenesis by Sertoli cells under the control of follicle-stimulating hormone (FSH) (but also requiring adequate testosterone).

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2
Q

How is LH and FSH suppressed by negative feedback in males?

A

Negative feedback suppression of LH is mediated primary by testosterone, while secretion of another hormone by the testis, inhibin, suppresses FSH.

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3
Q

When are testosterone levels the highest?

A

Testosterone levels are higher in the morning.

Therefore, if testosterone is marginally low on initial testing, sampling should be repeated in the early morning (0900hrs).

NB: There is no equivalent of the menopause in men, although testosterone concentrations decline slowly after the fourth decade onwards.

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4
Q

Explain the female hormone physiology of the menstrual cycle.

A

FSH stimulates growth and development of ovarian follicles during the first 14 days after the menses. This leads to a gradual increase in oestradiol production from granulosa cells, which initially suppresses FSH secretion (negative feedback) but then, above a certain level, stimulates an increase in both the frequency and amplitude of gonadotrophin-releasing hormone (GnRH) pulses, resulting in a marked increase in LH secretion (positive feedback).

The mid-cycle ‘surge’ of LH induces ovulation. After release of the ovum, the follicle differentiates into a corpus luteum, which secretes progesterone. Unless pregnancy occurs during the cycle, the corpus luteum regresses and the fall in progesterone levels result in menstrual bleeding.

Circulating levels of oestrogen and progesterone in pre-menopausal women are, therefore, critically dependent on the time of the cycle.

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5
Q

How would you test ovarian function in a pre-menopausal woman?

A

The most useful ‘test’ of ovarian function is a careful menstrual history: if menses are regular, measurement of gonadotrophins and oestrogen is not necessary.

In addition, ovulation can be confirmed by measuring plasma progesterone levels DURING THE LUTEAL PHASE (‘day 21 progesterone’).

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6
Q

What is the climacteric?

A

Cessation of menstruation (the menopause) occurs at an average age of approximately 50 years in developed countries. In the 5 years before, there is a gradual increase in the number of anovulatory cycles and this is referred to as the climacteric.

Oestrogen and inhibin secretion falls and lack of negative feedback results in increased pituitary secretion of LH and FSH (typically to levels above 30 U/L [3.3 microg/L]).

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7
Q

What is ‘delayed puberty’?

A

Puberty is considered to be delayed if the onset of the physical features of sexual maturation has not occurred by a chronological age that is 2.5 standard deviations (SD) above the national average. If the UK, this is by the age of 14 in boys and 13 in girls.

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8
Q

What is the difference between hypogonadotrophic hypogonadism and hypergonadotrophic hypogonadism?

A
  • -> HYPOgonadotrophic hypogonadism - pathology is in the HYPOTHALAMUS / PITUITARY
  • -> HYPERgonadotrophic hypogonadism - pathology is in the GONADS
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9
Q

What are the causes of delayed puberty and hypogonadism?

A

1) CONSTITUTIONAL DELAY (‘clock is running slow’)

2) HYPOGONADOTROPHIC HYPOGONADISM
- Structural hypothalamic/pituitary disease- Funcitonal gonadotrophin deficiency
a) Chronic systemic illness (e.g. asthma, malabsorption, coeliac disease, cystic fibrosis, renal failure)
b) Psychological stress
c) Anorexia nervosa
d) Excessive physical exercise
e) Hyperprolactinaemia
f) Other endocrine disease (e.g. Cushing’s syndrome, primary hypothyroidism)
- Isolated gonadotrophin deficiency (Kallmann’s syndrome)

3) HYPERGONADOTROPHIC HYPOGONADISM
- Acquired gonadal damage
a) Chemotherapy / radiotherapy to gonads
b) Trauma / surgery to gonads
c) Autoimmune gonadal failure
d) Mumps orchitis
e) Tuberculosis
f) Haemochromatosis
- Developmental / congenital gonadal disorders

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10
Q

When would you perform a karyotype in children with delayed puberty?

A

A karytotype should be performed in all adolescents with HYPERgonadotrophic hypogonadism, to exclude Turner’s and Klinefelter’s syndromes, unless there is an obvious precipitating cause.

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11
Q

How can puberty be induced?

A

Puberty can be induced by using low doses of oral oestrogen in girls (e.g. ethinylestradiol 2microg daily) or testosterone in boys (testosterone gel or depot testosterone esters). Higher doses carry a risk of early fusion of epiphyses.

In children with constitutional delay, this ‘priming’ therapy can be discontinued when endogenous puberty is established, usually in less than a year.

In children with hypogonadism, the underlying cause should be treated and reversed if possible. If hypogonadism is permanent, sex hormone doses are gradually increased during puberty and full adult replacement doses given when development is complete.

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12
Q

What are some causes of primary amenorrhoea?

A
  • Delayed puberty
  • Endometrial hypoplasia
  • Vaginal agenesis
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13
Q

What is primary amenorrhoea?

A

Failure of menses to occur by age 16

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14
Q

What is secondary amenorrhoea? What are some potential causes of secondary amenorrhoea?

A

Secondary amenorrhoea describes the cessation of menstruation. This may be due to:

  • Pregnancy
  • Menopause
  • Hypogonadotrophic hypogonadism
  • Ovarian dysfunction - hypergonadotrophic hypogonadism, PCOS, androgen-secreting tumours
  • Uterine dysfunction: Asherman’s syndrome
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15
Q

What are some symptoms of oestrogen deficiency?

A
  • Vasomotor: hot flushes, sweating
  • Psychological: anxiety, irritability, emotional lability
  • Genitourinary: dyspareunia, urgency of micturition, vaginal infections
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16
Q

What are some common hormone abnormalities in PCOS?

A

Elevated LH, prolactin and testosterone levels with normal oestradiol are common in PCOS.

17
Q

How would you treat symptoms of oestrogen deficiency?

A

Women who have had a hysterectomy can be treated with oestrogen alone, but those with a uterus should be treated with combined oestrogen/progestogen therapy, since unopposed oestrogen increases the risk of endometrial cancer.

18
Q

Briefly discuss the risks and benefits of Hormone Replacement Therapy (HRT).

A

The Women’s Health Initiative suds (published in JAMA in 2002) found that administering HRT for 5 years to 10,000 women aged 50-79 prevents 5 hip fractures and 6 cases of colorectal cancer, while inducing 8 extra cases of breast cancer, 8 or pulmonary embolism, 7 of coronary heart disease and 8 of stroke. The risks increase with age.

19
Q

What is the duration of Hormone Replacement Therapy for patients with premature menopause?

A

In patients with premature menopause, HRT should be continued up to the age of ~50 years, but only continued beyond this age if there are continued symptoms of oestrogen deficiency on discontinuation.

20
Q

What are symptoms of male hypogonadism?

A
  • Loss of libido
  • Lethargy
  • Muscle weakness
  • Decreased frequency of shaving
  • Gynaecomastia
  • Infertility
  • Delayed puberty
  • Osteoporosis
  • Anaemia of chronic disease
21
Q

How would you investigate hypogonadotrophic hypogonadism?

A

Pituitary MRI

22
Q

How would you investigate male hypergonadotrophic hypogonadism?

A

Male patients with hypergonadotrophic hypogonadism should have the testes examined for cryptorchidism or atrophy, and a karyotype performed (to identify Klinefelter’s syndrome).

23
Q

What are some indications for testosterone replacement?

A

Testosterone replacement is indicated in younger men with significant hypogonadism to prevent osteoporosis and to restore muscle power and libido.

24
Q

What are some risks associated with testosterone replacement therapy?

A

Testosterone therapy can aggravate prostate cancer; PSA should be measured before commencing testosterone therapy in men older than 50 years and monitored annually thereafter. Haemoglobin concentration should also be monitored in older men, as androgen replacement can cause polycythemia. Testosterone replacement also inhibits spermatogenesis.

25
Q

What is the incidence of infertility?

A

Infertility affects around 1 in 7 couples of reproductive age.

26
Q

What proportion of cases of infertility are due to female factors? What proportion is due to male factors? What proportion is due to unexplained or ‘mixed’ factors?

A

34-40% of cases of infertility are due to female factors; 35-40% of cases are due to male factors; and 20-35% of cases are due to unexplained or mixed factors.

27
Q

What are some causes of infertility?

A
  • PCOS
  • PID (chlamydia, gonorrhoea)
  • Endometriosis
  • Previous sterilisation
  • Previous pelvic or abdominal surgery causing fallopian tube dysfunction
  • Fibroids
  • Previous treatment for cervical carcinoma
  • Asherman’s syndrome
  • Y chromosome microdeletions
  • Varicocele
  • Hypergonadotrophic hypogonadism
  • Hypogonadotrophic hypogonadism
  • Congenital abnormality of vas defers/epididymis
  • Male tubular dysfunction from previous STI (chlamydia, gonorrhoea)
  • Previous vasectomy