Reproductive endocrine disorders Flashcards
describe how the hypothalamic-pituitary-gonadal axis regulates reproduction in males and females, with emphasis on the inhibins
explain how ageing and obesity compromise fertility in males and females
outline the pathophysiology of PCOS and endometriosis
in reproductive endocrinology what do Pituitary hormones follicle stimulating hormone
(FSH) and luteinizing hormone (LH) promote
Pituitary hormones follicle stimulating hormone
(FSH) and luteinizing hormone (LH) promote germ
cell maturation and gonadal production of steroids and
inhibins
in reproductive endocrinology what do Gonadal steroids and inhibins suppress
Gonadal steroids and inhibins act in an endocrine
manner to suppress gonadotrophin (FSH/LH
production)
In ovarian hormone production what do Gonadotrophic hormones (FSH and LH)
promote
Gonadotrophic hormones (FSH and LH)
promote maturation and ovulation of ovarian
follicles – production peaks immediately prior to
ovulation
In ovarian hormone production what is the function of Inhibin A/B
Inhibin A/B levels fluctuate across the
menstrual cycle – inhibins act in an endocrine
manner to suppress pituitary FSH production
In ovarian hormone production what is the function of Progesterone
Progesterone is produced by the corpus luteum
and is important for the establishment and
maintenance of pregnancy
In ovarian hormone production what is the function of Oestradiol
Oestradiol is produced by the dominant follicle
and supports follicle maturation. Like inhibin,
also suppresses pituitary FSH production
In testis hormone production what does Gonadotrophic hormone LH promote
Gonadotrophic hormone LH promotes
androgen production in testicular Leydig cells
in testis hormone production what do FSH and androgens act on
FSH and androgens act on testicular Sertoli cells
to support spermatogenesis
What are inhibins
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
what is the difference between female and male inhbins
Females produce two major inhibin forms, inhibin AND inhibin B, whereas males only produce inhibin B
What can a loss of inhibin cause
- Loss of inhibin production leads to a surge in activin production, which causes gonadal tumours, and lethal cachectic wasting in mice
- Loss of inhibin activity leads to hyperelevated FSH, superovulation, pregnancy failure in female mice, but has little consequences for male reproduction (in the mouse)
- Loss of inhibin activity promotes fat accumulation in female mice
Define infertility
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
what is infertility in male and female
- 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
What are the 2 main causes of infertility in female and male
Female:
1. Endometriosis
2. PCOS
Male:
1. Varicoceles
2. Sperm abnormalities
How does age influences female fertility
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)
How does age influences male fertility
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
how does Diet influence ovarian function
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
how does Diet influence fertility in males
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
Explain the IVF complication Ovarian hyperstimulation syndrome
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
What is polycystic ovarian syndrome
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)
What is the polycystic ovarian syndrome (PCOS) pathophysiology
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
