Reproductive endocrine disorders

Question 1

describe how the hypothalamic-pituitary-gonadal axis regulates reproduction in males and females, with emphasis on the inhibins

Question 2

explain how ageing and obesity compromise fertility in males and females

Question 3

outline the pathophysiology of PCOS and endometriosis

Question 4

in reproductive endocrinology what do Pituitary hormones follicle stimulating hormone
(FSH) and luteinizing hormone (LH) promote

Answer 4

Pituitary hormones follicle stimulating hormone
(FSH) and luteinizing hormone (LH) promote germ
cell maturation and gonadal production of steroids and
inhibins

Question 5

in reproductive endocrinology what do Gonadal steroids and inhibins suppress

Answer 5

Gonadal steroids and inhibins act in an endocrine
manner to suppress gonadotrophin (FSH/LH
production)

Question 6

In ovarian hormone production what do Gonadotrophic hormones (FSH and LH)
promote

Answer 6

Gonadotrophic hormones (FSH and LH)
promote maturation and ovulation of ovarian
follicles – production peaks immediately prior to
ovulation

Question 7

In ovarian hormone production what is the function of Inhibin A/B

Answer 7

Inhibin A/B levels fluctuate across the
menstrual cycle – inhibins act in an endocrine
manner to suppress pituitary FSH production

Question 8

In ovarian hormone production what is the function of Progesterone

Answer 8

Progesterone is produced by the corpus luteum
and is important for the establishment and
maintenance of pregnancy

Question 9

In ovarian hormone production what is the function of Oestradiol

Answer 9

Oestradiol is produced by the dominant follicle
and supports follicle maturation. Like inhibin,
also suppresses pituitary FSH production

Question 10

In testis hormone production what does Gonadotrophic hormone LH promote

Answer 10

Gonadotrophic hormone LH promotes
androgen production in testicular Leydig cells

Question 11

in testis hormone production what do FSH and androgens act on

Answer 11

FSH and androgens act on testicular Sertoli cells
to support spermatogenesis

Question 12

What are inhibins

Answer 12

Inhibins are gonadally-derived protein hormones that negatively regulate pituitary production of FSH. Inhibins constrain FSH levels by antagonising receptor activation by structurally related activins

Question 13

what is the difference between female and male inhbins

Answer 13

Females produce two major inhibin forms, inhibin AND inhibin B, whereas males only produce inhibin B

Question 14

What can a loss of inhibin cause

Answer 14

1. Loss of inhibin production leads to a surge in activin production, which causes gonadal tumours, and lethal cachectic wasting in mice
2. Loss of inhibin activity leads to hyperelevated FSH, superovulation, pregnancy failure in female mice, but has little consequences for male reproduction (in the mouse)
3. Loss of inhibin activity promotes fat accumulation in female mice

Question 15

Define infertility

Answer 15

Disease of the male or female reproductive system defined by failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse

Question 16

what is infertility in male and female

Answer 16

• Male infertility is most commonly caused by problems in the ejection of semen (1), absence or low levels of sperm, or abnormal shape (morphology) and movement (motility) of the sperm.
• Female infertility may be caused by a range of abnormalities of the ovaries, uterus, fallopian tubes, and endocrine systems

Question 17

What are the 2 main causes of infertility in female and male

Answer 17

Female:
1. Endometriosis
2. PCOS
Male:
1. Varicoceles
2. Sperm abnormalities

Question 18

How does age influences female fertility

Answer 18

In females, follicle number and quality declines steeply from 35 years of age

Marks the start of the menopause transition – 10-year process

Disrupted follicle growth alters ovarian hormone and growth factor production, consequently influencing pituitary hormone production

Exacerbates disruptions to ovarian folliculogenesis, leading to anovulatory cycles and eventually, complete loss of ovarian function and menses

Spontaneous menopause can also be induced via iatrogenic causes (cancer treatments, oophorectomy)

Question 19

How does age influences male fertility

Answer 19

Testis function and sperm quality also reduce with age
Advanced paternal age is associated with lower pregnancy rates, higher risk of pregnancy loss, and with negative childhood health outcomes, particularly with higher incidence of congenital birth defects and disorders like achondroplasia, autism, schizophrenia, trisomy, and some types of cancers

Advanced paternal age negatively affects sperm parameters, sperm DNA integrity, telomere length, chromosomal structures, and epigenetic factors

Question 20

how does Diet influence ovarian function

Answer 20

Diet influences ovarian function via changes in leptin and insulin, which alters the bioavailability of oestradiol
(E2) and testosterone (T) by affecting production of SHBG (sex hormone-binding globulin) from the liver
Insulin can also function directly on the ovary

Question 21

how does Diet influence fertility in males

Answer 21

In males, being overweight and obese is associated with a higher prevalence of low ejaculate volume, sperm concentration and total sperm count
↑ leptin inhibits androgen production in Leydig cells of the testis, leading to ↓ T production
↑ fat content in overweight/obese males leads to ↑ aromatase enzyme, which converts T into E2, resulting in ↑ E2
↑ E2 downregulates T production via the HPG axis
Thus, ↑ fat can result in ↓ T and thereby ↓ spermatogenesis via ↑ leptin and ↑ E2

Question 22

Explain the IVF complication Ovarian hyperstimulation syndrome

Answer 22

Ovarian hyperstimulation syndrome occurs most often in women undergoing IVF (as many as 1 in 20 females)

An iatrogenic complication caused by excessive response to controlled gonadotrophic hormone stimulation (FSH or chorionic gonadotrophins)

Characterised by (often painful) enlargement of the ovaries owing to a large number of developing follicles, and consequently heightened serum oestradiol

Thought to be mediated by ovarian release of vascular endothelial factor a (VEGFA) which promotes angiogenesis and vascular permeability

Question 23

What is polycystic ovarian syndrome

Answer 23

Characterised by ovulatory dysfunction, polycystic ovaries AND hyperandrogenism

Polycystic ovarian morphology is characterized by enhanced central thecal–stromal volume and increased numbers of preovulatory follicles ringing the ovarian cortex

Associated with metabolic dysfunction, and an increased risk of T2D, gestational diabetes, and pregnancy related complications (vascular and CV events)

Question 24

What is the polycystic ovarian syndrome (PCOS) pathophysiology

Answer 24

Hyperandrogenism and hyperinsulinemia 2 key features of PCOS

Adipocyte hypertrophy, inflammation and ↑ cytokines, altered adipokines

Leads to lipid spillover, and lipid accumulation in other tissues (muscle, liver), and drives lipotoxicity

Leads to tissue-specific insulin resistance

Question 25

what is endometriosis

Answer 25

Endometriosis is a disease in which tissue similar to the lining of the uterus grows outside the uterus. It can cause severe pain in the pelvis and make it harder to get pregnant.

Question 26

what is endometriosis pathogenesis

Answer 26

Endometriotic lesions develop in a micro-environment of ↑ oestrogen but alsoprogesteroneresistance, via molecular processes that promote cellular adhesion and proliferation, systemic and localised steroidogenesis, localised inflammatory responses and immune dysregulation, and vascularization and innervation

Question 27

What is adenomyosis

Answer 27

Growth of endo tissue lining the uterus within the muscle wall – painful and often heavy bleeding (menorrhagia)
Often co-occurs with endometriosis and/or leiomyoma (uterine fibroids – benign tumours)
Like endometriosis, oestrogen-dependent

Question 28

how is gonadal hormone production coordinated

Answer 28

Gonadal hormone production is coordinated by cross-talk with the pituitary

Question 29

what does the loss of ovarian function at menopause disrupt

Answer 29

Loss of ovarian function at menopause disrupts HPG crosstalk and is associated with the onset of various
physiological insults (e.g, bone and muscle loss, fat accumulation, and cognitive impairments)

Question 30

what do inhibins do in females

Answer 30

Inhibins negatively regulate pituitary FSH production, ovulation rates and are crucial during pregnancy