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Phase 2: Reproduction, Nephrology and Urology > Lecture 3: Female reproductive endocrinology > Flashcards

Lecture 3: Female reproductive endocrinology Flashcards

1
Q

Which androgen hormones are important in the female reproduction?

A
  1. Oestrogens
  2. Progesterone
  3. Androgens
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2
Q

Steroid hormones are derived from enzymatic modification of?

A

Chloesterol

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3
Q

What is the function of aromatase?

A

Converts androgens into oestrogens

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4
Q

Circulating oestrogens are a mix of which two types?

A

Oestrone and oestradiol

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5
Q

Name these parts of the biosynthesis of steroid hormones?

A
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6
Q

Describe the production of Oestrone?

A

Secreted directly from ovary or converted from androstenedione

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7
Q

Describe the production of oestradiol?

A

Produced by the ovary, derived by direct synthesis in developing follicles or through conversion of oestrone (low levels of testosterone in women)

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8
Q

Oestrogens are involved in the development of female ___ sex characteristics

A

Secondary sex characteristics- refer to visible changes that mark adult maturation that is not the sexual organs themselves.

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9
Q

What androgens are produced by the ovary?

A
  1. Dehydroepiandrosterone (DHEA)- most abundant
  2. Androstenediol
  3. Small amount of testosterone
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10
Q

Except the ovary, which other part of the body is an important source of androgens in females?

A

Adrenal glands- which contributes approx half the daily production of androstenedione and DHEA

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11
Q

DHEA is a biological intermediate between ____ and ____?

A

Androgens and oestrogens

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12
Q

Androgen production in females come from which sources?

A

Adrenal cortex

Ovaries

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13
Q

What produces progesterone?

A
  1. Corpus luteum found in the ovary
  2. The adrenal glands
  3. The placenta during pregnancy
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14
Q

Why is progesterone so important?

A

Important for:

  • Endometrial development
  • Maintenance of pregnancy by stimulating the nutrient supply for the embryo prior to the placenta
  • Mammary gland development
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15
Q

Describe Congenital Adrenal Hyperplasia?

A
  • 21 -hydroxylase deficiency
  • This is important in the conversion from cholesterol into aldosterone and cortisol, hence aldosterone and cortisol are not being present.
  • Patient has ambiguous genitalia i.e. when the infant’s external genitals don’t appear to be clearly either male or female
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16
Q

Outline some clinical examples of conditions that are a results of the dysfunction of the biosynthesis of steroid hormones?

A
  • Aromatase deficiency
    • Not aromatase- which is important in the conversion of androgens to oestrogens.
  • Aromatase excess
    • Too much aromatase- causes the excessive conversion of androgens to oestrogens.
    • Results in the feminisation of the male genitalia
  • Congenital adrenal hyperplasia
    • Deficiency in 21- hydroxylase
    • Important in the formation of cortisol and aldosterone
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17
Q

The female reproduction is regulated by what?

A
  1. Hypothalamic-pituitary-ovarian axis
  2. Uterus
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18
Q

Describe the hypothalamic-pituitary-ovarian axis?

A

Hypothalamus: secretes gonadotrophin releasing hormone (GnRH)

GnRH stimulates the anterior pituitary

Anterior pituitary: secretes the gonadotrophins (FSH and LH)

FSH and LH stimulates the ovaries

Ovaries and placenta (in pregnancy): secrete steroid sex hormones (oestrogen and progesterone)

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19
Q

What are the gonadotrophin hormones and what structure produces them?

A

Follicle stimulating hormone (FSH)

Luteinising hormone (LH)

Produced by the anterior pituitary

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20
Q

What are the sex steroid hormones?

A

Oestrogen

Progesterone

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21
Q

What cells in the hypothalamus produce GnRH?

A

Neurosecretory cells

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22
Q

Describe the hypothalamus section of the hypothalamic-pituitary-ovarian axis?

A
  • Neurosecretory cells in the hypothalamus produce gonadotrophin releasing hormone (GnRH)
  • GnRH are secreted into the portal vessels
    • From the portal vessels it goes to the anterior pituitary
  • The secretion is in a pulsative manner (i.e. it is not continously produced)
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23
Q

Describe the anterior pituitary section of the hypothalamic-pituitary-ovarian axis?

A
  • GnRH that is released into the portal vessels binds to the GnRH receptors in the anterior pituitary
  • The anterior pituitary secretes FSH and LH
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24
Q

Describe the ovary section of the hypothalamic-pituitary-ovarian axis?

A
  • The FSH and LH released by the anterior pituitary stimulates the ovaries to produce oestrogen and progesterone and triggers follicle maturation.
    • Also stimulates the placenta during pregnancy.
  • The oestrogen and progesterone act on their target tissue in the reproductive tract.
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25
Q

Describe the process of how LH and FSH stimulates the production of oestrogen in the ovary?

A

In response to FSH and LH, the granulosa cells of the ovarian follicles convert androgens (androstenedione and testosterone) which are secreted by the thecal cells into oestrogens (oestrone and oestrogen) which pass into the bloodstream

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26
Q

The ___ cells of the ovarian follicles convert androgens (androstenedione and testosterone) which are secreted by the ___ cells into oestrogens (oestrone and oestrogen) which pass into the bloodstream

A

A) granulosa

B) theca interna

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27
Q

What is the role of FSH on the follicle maturation?

A

Initiates the recruitment of follicles

Stimulates the follicles to be secreted and supports their growth

Acts on the granulosa cells

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28
Q

The FSH acts on which cells of the follicle?

A

Granulosa cells

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29
Q

The LH acts on which cells of the follicle?

A

Theca cells

30
Q

What is the role of LH on the follicle maturation?

A

Supports the theca cells

LH spike midcycle to trigger ovulation

31
Q

What are the phases of the ovarian cycle?

A
  1. Follicular phase - preovulatory
  2. Ovulatory phase
  3. Luteal phase - postovulatory
32
Q

What are the phases of the uterine cycle?

A
  1. Proliferatory phase
  2. Secretory phase
  3. Menses
33
Q

What are the 3 phases of the uterine cycle?

A
  1. Proliferatory phase
  2. Secretory phase
  3. Menses phase
34
Q

Give an example of a cell that produces aromatase?

A

Granulosa cells in the follicle

35
Q

The follicular phase (in the ovarian cycle) happens at the same time at which phase(s) in the uterine cycle?

A

Follicular phase happens at the same time as the menses and proliferatory phase of the uterine cycle

36
Q

Name these hormones?

A
37
Q

What hormone is released from the hypothalamus in relation to the reproductive tract?

A

Gonadotropin Releasing Hormone (GnRH)

38
Q

What is the effect of follicular inhibin in the follicular phase?

A

Inhibits FSH release

39
Q

Why is the progesterone levels tested around day 21 of the menstrual cycle?

A

As this is when there is a peak in progesterone (due to the formation of the corpus luteum)

Good indicator to assess if ovulation has occured

This is the window of implantation (the uterus is ready to receive the embryo)

40
Q

List the stages of development for a developing follicle?

A

Primodiral follicle -> primary follicle -> secondary follicle -> teritary follicle

41
Q

In the luteal phase there is a rise in progesterone (around day 21) due to the?

A

Corpus luteum

Only if ovulation has occured

42
Q

Draw a diagram to indicate the levels of the following hormones during the menstruation cycle?

Oestrogen

Progesterone

LH

FSH

A
43
Q

Progesterone production is ___ during the follicular phase of the ovarian cycle?

A

Low

44
Q

Oestrogen production is ___ during the follicular phase of the ovarian cycle?

A

Rising due to conversion of androgens to oestrogens via aromatase.

As the follicle gets bigger and more developed, more oestrogen levels as the granulosa cells produce oestrogen

45
Q

Describe the characteristics of the primordial follicle?

A

1 layer of flattened follicular cells surrounding an occyte.

Simple structure.

Many of them- all in arrested states

46
Q

What is the reason(s) why FSH levels decrease more than LH levels during the follicular phase?

A
  • Oestradiol inhibits FSH secretion more than LH secretion.
  • Inhibin, hormone produced by the developing follicle, inhibits FSH secretion but not LH secretion.
47
Q

Describe what happens in the anterior pituitary during the period of time when the oesterodiol is providing the negative feedback loop?

A

The anterior pituitary is still producing LH and FSH (during the negative feedback) but cannot release it.

Therefore, when the feeedback is switched to positive, it releases this massive store (stored LH is released in massive amounts, usually over 36 to 48 h, with a smaller increase in FSH)

48
Q

What does the LH surge trigger?

A
  • Release of the oocyte
    • Stimulates enzymes that initiate breakdown of the follicle wall and release of mature oocyte within about 16 to 32 h
  • Triggers completion of the first meiotic division of the oocyte
49
Q

Compare the length of time for the proliferatory/follicular phase and the secretory/luteal phase?

A

The length of this secretory/luteal is the most constant, averaging 14 days

This is because the corpus luteum life span is 14 days.

The proliferatory/follicular phase varies in length (10-14 d)

50
Q

What does the corpus luteum secrete?

A

Primarily progesterone in increasing quantities, peaking at about 6 to 8 days after ovulation

Small amount of oestrogen- providing negative feedback to the GnRH, LH and FSH

51
Q

Under the influence of ____ from the anterior pituitary, the granulosa cells secrete oestrogen.

A

FSH

52
Q

the corpus luteum regresses to form the copus _?

A

copus albicans

53
Q

What causes the corpus luteum to regress?

A
  • Rising progesterone levels (from the corpus luteum) inhibit LH production.
  • Low levels of LH causes the corpus luteum regresses to form the copus albicans
  • As a result, both oestrogen and progesterone secretion are stopped, and menses begins.
54
Q

After the corpus luteum has regressed into the corpus albicans, what happens to the hormonal levels?

A
  • Oestrogen and progesterone secretion are stopped.
  • Without these hormones, the endometrial lining is not maintained, resulting in the onset of menstruation.
55
Q

Describe the steps that causes the onset of menstruation?

A
  • Progesterone levels rise (as a result of the corpus luteum)
  • The progesterone levels inhibit the LH production.
  • Without LH, the corpus luteum regressed into the corpus albicans.
  • The levels of mainly progesterone and oestrogen decline (as the corpus luteum no longer produces them)
  • Without these hormones, the endometrial lining is not maintained causing the onset of menstruation
56
Q

When does the corpus luteum peak?

A

Around day 21, this is the peak of progesterone production

57
Q

What is the function of the uterine glands?

A
  • The endometrium becomes secretory as a result of rising progesterone levels.
  • Uterine glands secrete glycogen, giving the embryo nutritional support as it yet has a blood supply.
58
Q

Describe the oestrogen levels in the secretory/luteal phase?

A

Start to rise (as the corpus luteum matures)

Peaks around day 21.

Not nearly as high a level as progesterone

59
Q

If implantation occurs, what happens to the corpus luteum?

A

If implantation occurs, the corpus luteum does not degenerate but remains

60
Q

Which hormone supports the corpus luteum if implantation occurs?

A

Supported by human chorionic gonadotropin that is produced by the developing embryo.

hCG rescues the corpu luteum from death

61
Q

The continuous use of progesterone alone (in uncombined oral contraceptive pill) does what to ovulation?

A

Does not always inhibit ovulation

62
Q

If the progesterone only pill (uncombined oral contraceptive pill) does not always inhibit ovulation. What is its mechanism to prevent fertilisation?

A

It causes changes in the cervical mucus, in the uterine endometrium, and in motility and secretion in the uterine tubes.

Other barriers in place to prevent fertilisation

63
Q

Give examples of abnormalities that result in the excess of reproductive hormones?

A

Polycystic ovarian syndrome

Granulosa cell tumour

Teratoma

64
Q

Give examples of abnormalities that result in the deficiency of reproductive hormones?

A

Hypogonadism- low function of the gonads

Turner’s syndrome- one normal X sex chromosome. No oestrogen is getting produced

Klinefelters syndrome- male XXY. Low testosterone and high gonadotrophins (FSH and LH)

Kallman’s syndrome (GnRH deficiency)

65
Q

Describe the clinical presentation of polycystic ovarian syndrome?

A
  • Often inferility
  • No ovulations
  • Lack of menses
  • Weight gain
66
Q

Describe the pathogenesis of polycystic ovarian syndrome?

A
  • Multifactorial condition.
  • Dysregulation in the release of GnRH
    • No longer pulsative release
  • Results in the increase of LH to FSH ratio
  • The high level of LH stimulates the theca cells to produce more oestrogen.
    • This causes the follicle to arrest.
67
Q

What must be the ratio of LH:FSH to be diagnostic of polycystic ovarian syndrome?

A

>2:1

LH: FSH

68
Q

Describe the appearance of the ovaries in polycystic ovarian syndrome when they are seen on an ultrasound scan?

A
  • The ovaries are found to have multiple, small cysts around the edge of the ovary.
  • These cysts are only a few millimetres in size.
  • The cysts are not actually cysts but have the appearance of cysts. They are actually partially developed eggs that were not released.
69
Q

How common and what causes polycystic ovarian syndrome?

A
  • Common endocrine abnormality
  • Approximately 1 in 5 women have polycystic ovaries
  • Doctors are still not entirely clear why some women have polycystic ovaries. There is often a hereditary link and a link with diabetes in the family.
70
Q

What are the treatments available for polycystic ovarian syndrome?

A
  • Weight loss
    • Loss of 5% body weight can have significant improvement in the condition
  • Contraceptive pill
    • Can induce regular “periods”
  • Metformin
    • Usually a drug for type 2 diabetes mellitus
    • It can also lower insulin and blood sugar levels in women with PCOS- insulin resistance is a common effect of PCOS.
    • Moreover, it encourage fertility- however not licensed for this use in the “UK”
  • Fertility treatment (if needed)
    • Clomifene: encourages the monthly release of an egg from the ovaries (ovulation).
    • IVF (rare)
71
Q

For polycystic ovarian syndrome, is it a failure of the ovary or due to a hormonal imbalance?

A
  • It is not a failure of the organ (ovary)
  • Hormonal imbalance
    • No negative feedback present
    • Oestrogen levels will stimulate the production of LH and FSH, causing an imbalance between LH and FSH.
    • High levels of LH will stimulate the production of androgens (by stimulating the theca cells)
72
Q

What is the action of human chorionic gonadotropin on the ovary?

A

Prevents disintegration of the corpus luteum

Phase 2: Reproduction, Nephrology and Urology (25 decks)

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