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PT4023 CA2 > L11 Sex Hormones > Flashcards

L11 Sex Hormones Flashcards

1
Q

Describe the hypothalamic-pituitary-gonadal axis

A

Human reproduction begins with secretion of GnRH from hypothalamus. GnRH stimulates FSH and LH release from pituitary. FSH and LH stimulate production of steroid hormones and gametes by the ovary and testes.

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2
Q

3 categories of steroids secreted by the gonads

A
  1. Oestrogens: oestradiol, estrone, estriol
  2. Progestins: progesterone
  3. Androgens: testosterone
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3
Q

Which enzyme is involved in the conversion of testosterone to dihydrotestosterone?

A

5α-reductase

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4
Q

Which enzyme is responsible for the conversion of testosterone to estradiol?

A

CYP19A1/aromatase

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5
Q

What is the main hormone in males?

A

total testosterone

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6
Q

What percentage of testosterone is produced by the testes?

A

95%

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7
Q

How does dihydrotestosterone affect external genitalia?

A

Dihydrotestosterone is responsible for differentiation during gestation, maturation during puberty, and adulthood prostatic diseases

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8
Q

How does testosterone affect internal genitalia?

A

Testosterone is responsible for Wolffian development during gestation

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9
Q

How does estradiol affect bone?

A

Estradiol significantly impacts bone density - why menopausal women experience changes in bone density, brittle bones, and increased risk of osteoporosis

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10
Q

The consequences of androgen deficiency depend on…

A

The stage of life during which the deficiency first occurs and the degree of the deficiency

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11
Q

Effect of androgen deficiency during foetal development

A
  • incomplete sexual differentiation
  • results only from testicular disease e.g. 17α-hydroxylase deficiency
  • complete deficiency results in entirely female external genitalia
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12
Q

Effect of androgen deficiency before completion of puberty

A
  • failure to complete puberty
  • pubertal changes impaired to a degree proportionate to the abnormality of testosterone secretion
  • if GH is normal when testosterone secretion is subnormal, long bones continue to lengthen (eunuchoid)
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13
Q

Effect of androgen deficiency after completion of puberty

A

i.e. after castration or anti-androgenic treatment
- regression of the pubertal effects of testosterone
- libido and energy decrease within a week or two, but other testosterone-dependent characteristics decline more slowly

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14
Q

Alkylated forms of testosterone

A
  • methyltestosterone
  • oxymetholone
  • fluoxymesterone
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15
Q

Disadvantages of oral alkylated forms of testosterone

A
  • associated with hepatopathy
  • have erratic absorption
  • decreased effectiveness compared to the intramuscular preparations
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16
Q

What oral testosterone therapy has a very short half-life and requires administration 2-3 times daily?

A

oral testosterone undecanoate (Andriol)

17
Q

Why are buccal testosterone tablets rarely used?

A

because they require twice daily usage and 5-10% of men experience significant gingival irritation

18
Q

What is oral testosterone/androgen therapy used for?

A

male hypogonadism

19
Q

4 intramuscular testosterone esters that are used clinically

A
  1. testosterone propionate
  2. testosterone enanthate
  3. testosterone cypionate
  4. testosterone undecanoate
20
Q

Classification of causes of male hypogonadism

A
  1. Hypothalamic-pituitary disorders e.g. panhypopituitarism
  2. Primary testicular abnormalities e.g. Klinefelter syndrome (XXY)
  3. Defects in androgen action e.g. complete/incomplete androgen insensitivity
21
Q

Causes of male infertility

A
  1. Endocrine e.g. hypothalamic-pituitary disorders, primary testicular disorders
  2. Defects in spermatogenesis e.g. idiopathic, drug-induced
  3. Sperm transportation defects e.g. ductal obstruction, retrograde ejaculation (often occurs in BPH)
  4. Sexual function disorders e.g. erectile dysfunction
  5. Miscellaneous e.g. varicocele
22
Q

Effect of GnRH agonists

A

promote follicle maturation

23
Q

Effect of GnRH antagonists

A

suppress LH surge

24
Q

What is Menotrophin?

A

A GnRH agonist that is used to treat infertility by providing LH and FSH to stimulate the ovaries

25
Q

What anti-oestrogen acts directly on the anterior pituitary?

A

Clomiphene

26
Q

What is Danazol?

A

An androgenic hormone that suppresses LH/FSH mid-cycle and is used to treat endometriosis and fibrocystic breast disease.

27
Q

What is amenorrhea?

A

Amenorrhea is defined as either the absence of menarche by age 16, or no menses for more than three cycles in an individual who has previously had cyclic menses.

28
Q

If the outflow tract is intact, amenorrhea is most likely the result of…

A

disruption in the HPO axis

29
Q

Classification of amenorrhea

A

primary or secondary, depending on whether the individual has experienced menses in the past

30
Q

Primary amenorrhea is more often associated with…

A

genetic and anatomic abnormalities

31
Q

Potential hormonal mediators of amenorrhea

A
  • Stress & Cushing’s disease increase CRH and therefore cortisol levels, which suppress GnRH release & LH responsiveness to GnRH
  • Low leptin levels & increased FGF-21 suppress GnRH release by decreasing kisspeptin expression
  • Increased TRH (hypothyroidism) stimulates PRL release, suppressing GnRH release
  • High androgen & progesterone levels (in CAH) likely suppress GnRH release
32
Q

Amenorrhea categories

A
  1. Absent breast development; uterus present
    - e.g. gonadal failure, defects in oestrogen biosynthesis, pituitary failure
  2. Breast development; uterus absent
    - e.g. androgen resistance, congenital absence of uterus
  3. Absent breast development; uterus absent
    - e.g. defects in testosterone biosynthesis
  4. Breast development; uterus present
    - e.g. pregnancy, hypothalamic aetiology
33
Q

What accounts for >30% of cases of amenorrhea and up to 75% of all cases of anovulation?

A

hyperandrogenic anovulation (most often due to PCOS)

PT4023 CA2 (6 decks)

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