Gonads Flashcards

The gonads: explain the stages of gametogenesis in male and female gonads; recall the principle structures of the testes and ovaries and their function Sex hormones: explain the process and regulation of steroidogenesis in male and female gonads, recall the physiological actions of male and female gonadal steroids; recall the hypothalamo-pituitary gonadal axis and its regulation in males and females Menstrual cycle: recall the phases of the menstrual cycle and the physiological changes that oc

1
Q

What is the definition of a gonad?

A

Organ that produces the gamete.

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2
Q

What are the two gonads?

A

Testes and ovaries.

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3
Q

What is the basic embryology of the gonads?

A

Develop from the same undifferentiated structure. Genes on the Y chromosome (SRY gene) are key to the differentiation of the gonads into testes. Without it, ovaries will develop.

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4
Q

What are the two major functions of the gonads? Alternative name for each.

A

PRODUCTION OF GAMETES for reproduction. Also called GAMETOGENESIS. PRODUCTION OF STEROID HORMONES. Also called STEROIDOGENESIS.

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5
Q

Gametogenesis: what’s the process in males and females?

A

IN MALES: Spermatogenesis – production of mature spermatozoa. IN FEMALES: Oogenesis – production of ripe ova.

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6
Q

Steroidogenesis: what’s the process in males and females?

A

IN MALES: Androgens, and small quantities of oestrogens and progestogens. IN FEMALES: Oestrogens and progestogens, and small amounts of androgens.

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7
Q

What is an androgen?

A

Any steroid hormone that regulates the development and maintenance of male characteristics by binding to androgen receptors.

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8
Q

Examples of androgens? (x1)

A

Testosterone

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9
Q

What is the stem cell that gives rise to gamete cells in both sexes?

A

Primordial germ cells.

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10
Q

Describe how the number of germ cells in MALES fluctuates throughout life – from conception? What is the name of the immature germ cell we are looking at – explain what they are? Mention one key number.

A

Spermatogonia – immature germ cell produced at an early stage during embryogenesis, in the wall of seminiferous tubule in the testes.

They proliferate by mitosis in these tubules – number around 6 to 7 million. Levels remain fairly consistent throughout life but declines slightly in later life.

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11
Q

Describe how the number of germ cells in FEMALES fluctuates throughout life – from conception (including one specific timing)? What is the name of the immature germ cell we are looking at – explain what they are? Mention two key numbers.

A

Oogonia – immature germ cell produced at an early stage during embryogenesis.

In females, these germ cells proliferate my mitosis, hence there’s a quick increase. The numbers peak to around 5-6 million at around 24 weeks gestation.

Before birth, most oogonia have either degenerated (atresia) or differentiated into primary oocytes, hence the number of oogonia fall. Atresia is initially very fast.

Primary oocytes will then undergo meiosis but are then arrested at prophase I until puberty.

Numbers have fallen to around 2 million by birth.

Numbers continue to deplete from birth until there is none left, and menopause is induced.

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12
Q

What happens in the process of spermatogenesis? Time-scale?

A

Germ cell differentiates into spermatogonia in very early life. This germ cell is diploid (SO WILL DEVELOP INTO 4 sperm).

Spermatogenesis doesn’t actually start UNTIL PUBERTY. Spermatogenesis– process occurs in conjunction with the immature germ cell dissociating from the basal lamina of the tubule.

In puberty, release of hormones including testosterone means spermatogonia mitotically divide – half are kept as spermatogonia, the other half become primary spermatocytes.

Primary spermatocytes undergo their first meiotic division to secondary spermatocytes which are HAPLOID.

These undergo their second and final meiotic division to give spermatids which are haploid and contain 23 chromosomes in each.

The spermatid undergoes further maturation to form Spermatozoa. The process is called spermiogenesis and when the spermatid develops a tail, acrosome, and mitochondria neck region…

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13
Q

Alternative name for spermatogenesis?

A

Can also be referred to as male gametogenesis.

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14
Q

How many sperm are produced a second?

A

300-600.

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15
Q

What happens in the process of oogenesis? Time-scale?

A

Germ cell differentiates into oogonia in embryogenesis. Oogonia are diploid.

Mitosis of oogonia produces some oogonia which undergo atresia, while others form primary oocytes – also diploid. Primary oocyte is an immature ovum that undergoes growth and some maturation (some follicle cells grow around the oocyte to form a primary follicle. During embryogenesis, the primary oocyte also begins meiosis, but stopped during prophase I.

Ovaries become inactive. During puberty, the primary oocytes continue their meiotic division and the follicle continues to grow as a result of hormonal changes.

The first meiotic division occurs asymmetrically – this still produces two cells with the same number of chromosomes in each, it’s just the actual cell that is split differently so one is bigger than the other.

This produces a ‘first polar body’ (which immediately degrades), and a secondary oocyte.

The secondary (haploid) oocyte is the precursor of an egg. They complete their development into an ovum if fertilised by a sperm cell. In their final meiotic division, they divide asymmetrically to produce a second polar body and an ovum that has a large cytoplasm because of the asymmetrical process.

The rest of the oocytes remain dormant, and supplies remain until they run out and menopause happens.

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16
Q

Where are gonadotrophins produced?

A

Anterior pituitary gland.

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17
Q

What hormones in men increase during puberty?

A

At puberty, there is increased secretion of gonadotrophins in the pituitary and testosterone in the testis.

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18
Q

What does testosterone do? (x3)

A

Gives secondary male sexual features e.g. facial hair. Maturation ad development of the testis. Maturation of the seminiferous tubules which allows spermatogenesis.

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19
Q

What is the structure of the male gonad?

A

Note that tubules are coiled. Note also that the epididymis is highly coiled. Both for higher surface area and greater storage. Remember that for the tubules, the immature germ cells are associated to the basal lamina, so need a large surface area.

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20
Q

Where do the male germ cells go in relation to the testes anatomy, as they develop and mature?

A

Spermatids collect into the lumen of the seminiferous tubules and drained by the vasa efferentia into the epididymis. Epididymis is where spermatids are stored and nutrients are secreted for maturation into spermatozoa. Eventually expelled by vas deferens by the smooth muscle into the urethra.

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21
Q

What is the structure of a seminiferous tubule – cross section?

A

Layered into: lumen, Sertoli cell, basal lamina. Sertoli cells form gap junctions.

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22
Q

Where are TESTICULAR androgens produced specifically? (x2 points)

A

Leydig cells. Found adjacent to the seminiferous tubules.

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23
Q

How are Leydig cells stimulated to produce AND secrete testicular androgens (mainly?)?

A

Stimulation of LH receptors on the Leydig cells by LH (a gonadotrophins) – stimulates production and secretion of testicular androgens, mainly testosterone.

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24
Q

How do spermatogonia move within the seminiferous tubules during maturation and division?

A

Spermatogonia migrate towards the lumen via their own special mechanism. They develop partly in the Sertoli cell metabolism – this is how they pass the tight junction. They emerge as spermatids into the lumen, and cannot re-associate with the basal membrane because of the tight junctions between the Sertoli cells.

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25
Q

What is the significance of the tight junctions between the Sertoli cells? (x2)

A

Keep spermatids in the lumen of the tubules. Forms a blood-testes barrier.

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26
Q

What receptors do the Sertoli cells contain? (x2)

A

FSH receptors and androgen receptors.

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27
Q

What are the purposes of the receptors of Sertoli cells? (x2)

A

Control spermatogenesis. FSH receptors detect when FSH high and produce inhibin as well as other molecules. Inhibin reduces FSH levels in the blood by affecting the pituitary (and hypothalamus). This is a negative feedback system that control FSH levels – FSH decreases levels of sperm cells.

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28
Q

In the ovaries, what would it look like in terms of the processes going on?

A

Ovaries also – obviously – contain oocytes from birth with one or some layers of follicular cells around them.

In gametogenesis, the dominant follicle is selected and it grows into the GRAAFIAN follicle. All remaining follicles that are stimulated to grow from FSH undergo atresia (degradation). Once the ovum is released, the remaining follicular cells turn into a corpus luteum

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29
Q

What is the structure of the GRAAFIAN follicle? (x4) Characteristics? (x2)

A

Closest point to ovulation. Maximum size has been reached. Follicle contains ovum, located inside a follicular fluid which is very large in the Graafian follicle. This is surrounded by granulosa cells (follicular cells), and thecal cells (endocrine follicular cells that have roles including synthesising androgens and signal transductions).

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30
Q

What does the corpus luteum do? (x1)

A

Temporary endocrine function that produces high levels of progesterone.

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31
Q

What are steroid hormones synthesised from?

A

Cholesterol.

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32
Q

What determines what cholesterol will be synthesised into? Why?

A

The tissue location. Adrenals or gonads. Because it depends on the enzymes present in the tissue.

33
Q

What steroid hormones are produced in the adrenals and gonads? (x3 ad x3)

A

ADRENALS – Mineralocorticoids, glucocorticoids, some androgens. GONADS – Progestogens (C21), Androgens (C19), Oestrogens (C18).

34
Q

List one example of a mineralocorticoid and a glucocorticoid. And an androgen produced in the kidney – what does it do?

A

Aldosterone and cortisol respectively. Androgen = androstenedione. Very weak androgen produced in the adrenals AND gonads. (In the gonads, this is converted into the more potent androgen, testosterone.)

35
Q

What is the process of steroidogenesis in the male and female gonads? Points to be made about testosterone and relative androgen strengths.

A

NB: only refer to the processes involving the gonads. No need to know processes involving the adrenals. Androstenedione is a weak androgen. Testosterone more potent androgen. Dihydrotestosterone also more potent.

36
Q

Where in the gonads is testosterone converted into DHT, and where is it converted into oestrogen? What are the processes called?

A

DHT: REDUCTION (hence why 5alpha-reductase) in the SEMINIFEROUS TUBULES and PROSTATE. Oestrogens: AROMATISATION (hence why aromatase) in the SERTOLI CELS.

37
Q

What enzymes are involved in the synthesis of steroid hormones in the gonads? (x8)

A

Cholesterol to pregenolone: P450 side-chain cleavage enzyme

Pregenolone to preogesterone: 3-beta-hydroxysteroid dehydrogenase.

Progesterone to 17-OH progesterone to androstenedione: 17,20-lyase

Androstenedione to testosterone: 17-beta-hydroxysteroid dehydrogenase.

Testosterone to dihydrotestosterone: 5alpha-reductase

Androstenedione to oestrone: Aromatase

Testosterone to 17B-oestradiol: Aromatase

Oestrone to 17B-oestradiol: 17B-hydroxysteroid dehydrogenase.

38
Q

How is testosterone and DHT transported in the blood?

A

By Sex hormone binding globulin (SHBG), Albumin, and some free.

39
Q

How is testosterone and DHT transported in the seminiferous fluid?

A

Androgen binding globulin (ABG).

40
Q

How long does the menstrual cycle last?

A

28 days. But can vary.

41
Q

What is historically considered the first day of menstruation?

A

Loss of blood and cellular debris from necrotic uterine epithelium.

42
Q

When does ovulation occur?

A

Day 14.

43
Q

What two cycles are involved in the menstrual cycle? And their locations.

A

Ovarian cycle (occurs in the ovaries). Endometrial cycle (occurs in the uterus).

44
Q

What occurs in the ovarian cycle? (x3 phases) When do each occur?

A

Follicular phase (follicles in the ovary mature. This occurs when LH levels fall and FSH is high.) – from Day 1. Ovulation – Day 14. Luteal phase (oestrogen and progesterone increase and prepare the endometrium to accept an embryo) - until Day 1 OR, as soon as menstruation begins.

45
Q

What happens in the endometrial cycle? (x2)

A

Proliferative phase – endometrium builds up and thickens. Secretory phase – (after ovulation) – corpus luteum secretes progesterone which stimulates development of glands and arteries in the endometrium, causing it to become thick and spongy.

46
Q

How does the ovarian cycle influence the endometrial cycle? (x2)

A

In follicular phase, oestrogen rises (17B-oestradiol), which has a proliferative effect on the endometrium. It does this by causing implantation of more oestrogen and progesterone receptors into the endometrium (progesterone receptors are for later in the menstrual cycle). In the luteal phase, 17B-oestradiol and progesterone levels increase (again). Progesterone removes oestrogen receptors from the endometrium and create a more ideal environment for egg implantation.

47
Q

What are the phases of the menstrual cycle? (x5)

A

Early follicular phase. Early-mid follicular phase. Mid-follicular phase. The late follicular phase. Luteal phase.

48
Q

What happens in the early follicular phase?

A

Menstrual bleeding. FSH levels are raised at this time. Between 8 and 10 follicles start to mature and grow. They compete to become the dominant follicle. They are growing under the regulation of FSH.

49
Q

What happens in the early-mid follicular phase?

A

FSH and LH stay the same, while levels of oestrogen (oestradiol) rise. In this stage, one follicle gets bigger than the rest – dominant follicle. Higher levels of oestradiol are therefore produced. These increased levels have a positive feedback effect on the granulosa cells around it. Oestradiol results in increased growth of the granulosa cells, so my oestrogen can be synthesised.

50
Q

What happens in the mid-follicular phase?

A

We now have a dominant follicle called a Graafian follicle that has developed. This causes very high levels of oestrogen. This has a negative feedback effect on the pituitary and hypothalamus which results in reduced levels of gonadotrophins (FSH and LH). Graafian follicle no longer relies on the FSH and LH, so remaining follicles undergo atresia.

51
Q

What happens in the late-follicular phase?

A

High oestradiol – at a point – results in POSITIVE feedback on the GnHR (in the hypothalamus), and LH (in the pituitary). There is also a small surge in FSH. Results in ovulation and release of the ovum from the follicle, into the Fallopian tube. There is a small increase in the progesterone 17OH-progesterone, which enhances the positive feedback effect that results in the surge of gonadotrophins.

52
Q

What happens in the luteal phase?

A

Follicle that remains after ovulation transformed to corpus luteum. Continue to produce oestrogen, and lots of progesterone. These both negatively feedback on the gonadotrophins to keep those levels low. The progesterone prepares the endometrium for implantation by a fertilised egg.

53
Q

What is E2?

A

An oestrogen. It usually refers to 17B-oestrodial.

54
Q

What happens to hormone levels if fertilisation does not occur?

A

Indirect and direct negative feedback. If fertilisation DOES NOT occur, oestrogen, progesterone and inhibin exert a negative feedback effect on the LH and FSH (in the pituitary and hypothalamus). LH and FSH rise and the cycle starts again. The corpus luteum involutes (called luteolysis), progesterone and oestrogen levels fall, and menstruation occurs.

55
Q

What happens to body temperature in the menstrual cycle – what causes the change?

A

There is an increase in body temperature because of the increase in progesterone levels in the luteal phase.

56
Q

What is the nature of follicle maturation right the way through life? What are the two fates of the product?

A

Follicles selected spontaneously for further development right through life (including embryogenesis). They are selected independent of gonadotrophin and form pre-antral follicles.

If they form pre-antral follicles when FSH levels are not raised, they undergo atresia.

If they form pre-antral follicles when FSH levels are raised, they go on to develop further and are the dominant follicles.

57
Q

What happens when pre-antral follicles mature and grow further? (x4 stages)

A

The follicle gets larger and there is now an antrum – fluid-filled space. Called the EARLY ANTRAL FOLLICLE.

The thecal and granulosa cells grow and more oestrogen is therefore secreted. Called the LATE ANTRAL FOLLICLE. At this point, if there are still multiple follicles, the dominant one will be selected and others will enter atresia.

Then you have the GRAFFIAN FOLLICLE, which has a large fluid-filled space, and the ovum is embedded in the walls of the follicle.

Ovulation!

58
Q

How does the corpus luteum go on to produce progesterone and oestrogen?

A

Granulosa cells proliferate and enlarge and get invaded by blood vessels. They continue to express FSH and LH receptors. Increased levels of LH and FSH (from ovulation) therefore result in production of a large amount of progesterone and oestrogen.

59
Q

How is steroidogenesis triggered in the ovaries?

A

Thecal cells have LH receptors on them. Stimulate steroidogenesis and androgens are produced. Only androgens are produced though because the thecal cells have no aromatase. The androgens diffuse therefore, into the granulosa cells where aromatase and FSH receptors are present. FSH stimulates those receptors and the aromatase = 17B-oestradiol is produced. The same process occurs in the corpus luteum. So essentially, androgens are only an intermediate in females – they are a substrate for oestrogen synthesis – hence why they are in low levels in women!

60
Q

What is the function of androgens in the fetus? (x2)

A

Development of male internal and external genitalia. Fetal growth (acting with other hormones).

61
Q

What is the function of androgens in adults? (x5)

A
  1. Needed for spermatogenesis. 2. Growth and development of male genitalia AND secondary sex characteristics (e.g. facial hair). 3. Protein and bone anabolism i.e. muscle and bone growth. 4. Behavioural: male sexual behaviour. 5. Pubertal growth spurt (with Growth Hormone) …The functions are listed in decreasing importance.
62
Q

List oestrogens. (x3)

A

17B-oestradiol. Oestrone (precursor) Oestriol (pregnancy)

63
Q

What are the effects of oestrogens reproductively? (x2)

A
  1. Endometrium: stimulates proliferation. 2. Menstrual cycle: triggers LH surge resulting in ovulation.
64
Q

What are the somatic effects of oestrogen? (x4)

A

Feedback regulation on GnRH (negative (and positive in ovulation)). Stimulates osteoblasts. Metabolic actions e.g. on lipids. Behavioural effects – maternal behaviours (discussed previous Endocrinology topic).

65
Q

List examples of progestogens. (x2)

A

Progesterone 17alpha-hydroxyprogesterone.

66
Q

What are the effects of progestogens? (x4)

A

Stimulates secretory activity in endometrium and cervix – development of glands and arteries. Removes oestrogen receptors from the endometrium. Enhances the positive feedback effect that results in the surge of gonadotrophins in ovulation. Negatively feedback on the gonadotrophins (hypothalamic GnRH).

67
Q

Summary: what does FSH do? (x3)

A
  1. Causes selection and maturation of follicles.
  2. Causes production of oestrogen (and progesterone) in the follicles. FSH is responsible for this production because the follicles that FSH stimulates the ovaries produce, themselves produce these hormones (developing follicles produce oest. and prog.) i.e. no FSH means no developing follicles, which means no oestrogen and progesterone production.
  3. Produces Inhibin, which inhibits FSH.
68
Q

Summary: what does LH do? (x3)

A

LH triggers enzymes which break down the follicle to release the egg. It stimulates it to form the corpus luteum and produce progesterone = Causes ovulation.

Causes production of androgens (and progesterone) in the follicles.

Suppressed by oestrogen. However, when oestrogen is high enough and lasts for long enough, LH also stimulated.

69
Q

Recall the hypothalamo-pituitary-testicular axis. (x5 points about how the axis works in general, x2 points about how the axis is regulated).

A

Hypothalamic pulse generator releases GnRH in pulses every hour or two. This triggers pulses in the production and secretion of FH and LSH in the anterior pituitary. LH stimulates ANDROGEN PRODUCTION in the testis: LH binds to receptors on the Leydig cells which stimulates them to make testosterone (virilisation = development of male characteristics). FSH stimulates GAMETE PRODUCTION in the testis: binds to receptors on the Sertoli cells which line the seminiferous tubules, which stimulates spermatogenesis. Testosterone also interacts with the FSH pathway – it is needed for the final stage of spermatogenesis.

Testosterone negatively feedbacks on the hypothalamus and anterior pituitary. Inhibin (produced by the Sertoli cells (stimulated by the FSH) negatively feedbacks on the hypothalamus and anterior pituitary. SO, BOTH INHIBIT FSH AND LH.

70
Q

Recall the hypthalamo-pituitary-ovarian axis.

A

Hypothalamic pulse generator releases GnRH in pulses every hour or two. This triggers pulses in the production and secretion of FH and LSH in the anterior pituitary.

71
Q

What is amenorrhoea?

A

Absence of menstrual cycles.

72
Q

What is the difference between primary and secondary amenorrhoea?

A

Primary: if a woman has never had a period in their life. It occurs when you’re born without the hormones needed, so never reach puberty and need drug therapy. Secondary: if a woman has had period which then stop.

73
Q

What is oligomenorrhoea?

A

Infrequent menstrual cycles.

74
Q

What is infertility defined as?

A

Couple cannot get pregnant following 12 months of regular unprotected sex.

75
Q

What are the causes of infertility? (x5)

A

PITUITARY FAILURE: e.g. tumour means that FSH and LH will not be made, so testosterone will not be made for male genitalia, and spermatogenesis will not occur in men, and women will not undergo menstruation.

PROLACTINOMA: pituitary tumour that results in excess production of prolactin, which inhibits FSH and LH.

TESTICULAR FAILURE: causes – e.g. mumps, Klinefelter syndrome (XXY) (results in small testicles).

OVARIAN FAILURE: causes – e.g. Turner syndrome (XO) (completely missing an X chromosome). POLYCYSTIC

OVARIAN SYNDROME (increased number of enlarging ovarian follicles).

76
Q

CASE STUDY: Patient is female, has headaches, loss of peripheral vision, tiredness, oligomenorrhea, occasional expression of milk from the breasts. Oestrogen, progesterone, FSH and LH levels are all low. What does the patient have? How does this explain the symptoms?

A

Patient has pituitary adenoma (tumour) affecting prolactin production. Prolactin inhibits LH and FSH secretion.

Headaches: overgrowth (even small) can increase pressure enough to cause pain.

Galactorrhoea (lactating): stimulated by excess prolactin.

Loss of peripheral vision: see photo.

77
Q

What if a pituitary tumour is really big?

A

Can put pressure on the optic nerve so much that there is death – not just peripheral vision loss.

78
Q

How does prolactin inhibit FSH and LH production?

A

Neurones in the hypothalamus produce kisspeptin (in addition to the hormones that affect the pituitary). Kisspeptin regulates GnRH. These neurones have prolactin receptors. If there’s too much prolactin, the system closes down and GnRH decreases, so FSH and LH levels fall, so oestrogen and progesterone levels also fall.