Reproductive endocrinology Flashcards
Reproductive
Endocrinology
Reproductive endocrinology:
The study of hormones involved in reproduction and the development and function of reproductive organs.
Steroidal Hormone
Steroidal hormone:
A hormone derived from cholesterol, including sex hormones such as androgens, oestrogens and progesterone.
Androgens
Androgens:
Male sex hormones that are critical for sexual differentiation and the development of male characteristics.
Dihydrotestosterone (DHT)
Dihydrotestosterone (DHT):
An androgen that is critical for sexual differentiation in embryos and the maintenance of masculine characteristics.
Testosterone
Testosterone:
An androgen that is critical for sperm generation and the development and maintenance of masculine characteristics.
Oestrogens
Oestrogens:
- Secreted from the ovaries
- Stimulate uterine lining thickening
- Stimulate follicular development
- May inhibit or stimulate FSH or LH release depending on the part of the cycle
Female sex hormones that control the development and maintenance of feminine characteristics and stimulate egg follicle growth ,uterine lining thickening.
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Progesterone
Progesterone:
- Female sex hormones that stimulate the growth of the endometrial lining of the uterus for implantation.
- Released from the empty follicle an egg is released from
- Remains high during pregnancy if egg is released
- Maintains the uterine linking for foetal growth and promotes adaptation for pregnancy
- Increases mucus production at cervical to reduce infection risk and prevent sperm entry
- Inhibits, GNRH, FSH and LH release
Hypothalamic – pituitary axis
Hypothalamic – pituitary axis
The regulatory system that controls the synthesis and release of sex hormones, involving the hypothalamus, pituitary gland and gonads.
Gonadotropin-releasing Hormone (GnRH)
Gonadotropin-releasing Hormone (GnRH):
-synthesized and secreted by the hypothalamus
- stimulates the release of FSH (follicle-stimulating hormone) and (LH) luteinizing hormone.
Follicle-Stimulating Hormone (FSH)
Follicle-Stimulating Hormone (FSH)
- synthesized and secreted from the anterior pituitary gland
- acts on the female gonads to promote sex hormone production and gametogenesis,
- initiates follicular growth.
- stimulates oestrogen release
- stimulates egg maturation
Lutenizing Hormone (LH)
Lutenizing Hormone (LH):
• Secreted from the anterior pituitary gland
• Triggers ovulation
• Converts the follicle into the corpus luteum
- stimulates inhibit release from the ovaries
- levels spike mid cycle
- stimulates follicle development
The menstrual cycle
The menstrual cycle
The 28+/- 4 days cycle of oocyte release and the preparation and shedding of the uterine lining.
Follicular phase
Follicular phase
The phase of the menstrual cycle where the follicle grows and develops into a mature follicle
Ovulatory phase
Ovulatory phase
The phase of the menstrual cycle where the oocyte is released from the ovary.
Luteal phase
Luteal phase
The phase of the menstrual cycle where the corpus luteum develops from the follicle.
- Corpus luteum acts as controller of the uterine environment
- Fertilization occurs: maintenance of a suitable environment for pregnancy or implantation
- No fertilization: uterine lining breakdown
Polycystic ovary syndrome (PCOS)
Polycystic ovary syndrome (PCOS)
* Hormonal disorder affecting the ovaries,
* Characterized by excessive testosterone production and high level of insulin.
* PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses.
* Linked to infertility: anovulatory, infrequent periods, oligorrhoea.
* Linked to obesity and family history
* Abdominal fat deposition linked to insulin resistance
* Insulin resistance inhibits synthesis of sex hormone binding globulin in the liver and SHBG deficiency increases androgens
* L-carnitine and co-enzyme Q may help infertility
* Symptoms include irregular periods, difficulty getting pregnant, excessive hair growth, weight gain, and other related complications.
* Weight loss linked to: reduced hirsutism, partial menstrual cycle restoration, reduced insulin concentrations, reduced testosterone concentrations
Symptoms of polycystic ovary syndrome
Symptoms of polycystic ovary syndrome
* irregular periods
* difficulty getting pregnant
* Anovulation (lack or absence of ovulation)
* hirsutism,
* weight gain
* abdominal fat deposition (connected to insulin resistance)
* acne
* fluid filled sacs or cysts
* alopecia
What should PCOS treatment be?
- PCOS treatment should be symptom-oriented, long term and dynamic and adapted to the changing circumstances, personal needs and expectations of the individual patient
- Therapeutic approaches should target hyperandrogenism, the consequences of ovarian dysfunction and/or the associated metabolic disorders.
PCOS symptom management
PCOS symptom management:
symptoms can be managed through lifestyle changes, such as a healthy diet, regular exercise, weight loss, and medical interventions.
Is there a cure for PCOS?
There currently isn’t a cure for PCOS.
How is PCOS diagnosed?
PCOS diagnosis:
* PCOS is typically diagnosed through an ovarian scan trying to conceive.
* NIH, 2012:
Two of the three criteria and phenotype identification are required:
1. Hyperandrogenism (HA)
2. Ovulatory dysfunction (OD)
3. Polycystic Ovarian Morphology
II Ovulatory phase
II Ovulatory phase
Pituitary hormone effects:
LH and FSH stimulate maturation of the one of growing follicles.
Ovarian hormone effects:
Growing follicles begin to produce high levels of oestradiol, which:
* Stimulate GnRH secretion by the hypothalamus.
LH (Great spike in LH, LH spike) and FSH levels rise, resulting in ovulation.
* Cause the endometrium thicken.
* Release of egg from the ovary
Oestradiol
Oestradiol:
- Type of oestrogen
- Steroid hormone
- May inhibit or promote the secretion of LH and FSH depending on the point in the cycle
I Follicular phase
Follicular phase: Days 1-14
- From the first day of menstruation (day 0) until the beginning of ovulation (day 14)
Pituitary hormone effect:
LH and FSH stimulate several follicles to growth.
Ovarian hormone effects:
Follicles produce low levels of oestradiol that:
* Inhibit GnRH secretion by the hypothalamus, keeping LH and FSH low.
* Cause endometrial arteries to constrict resulting in
menstruation.
What is Anti-Müllerian hormone (AMH)?
Anti-Müllerian hormone (AMH):
a peptide growth factor of the transforming growth factor-β family, is a reliable marker of ovarian reserve.
Metformin as PCOS treatment
Metformin as PCOS treatment:
- Typically used for T2D
- Treats insulin resistance
- Improves ovulation
- May reduce androgen production (even in non -obese women)
- May prevent endometrial cancer: inhibits proliferation and invasion of endometriosis and non-endometriosis endometrial cancer cells. Might promote tumour cell apoptosis.
Associated with reduced risk of endometrial cancer.
- Safe for use during pregnancy
Oral contraceptive: Combined pill
Oral contraceptive: Combined pill
(COC e.g. progesterone, oestrogen)
• Decrease Androgen production
• Break continuous oestrogen
• Decrease risk of endometrial cancer
• Corrects abnormal bleeding
Oral contraceptive: Progesterone
Oral contraceptive: Progesterone
10-14 days a month
• Regulates menstrual cycle
• Prevents endometrial cancer
• Does not improve androgen levels
Clomiphene Citrate (Clomid or Serophene)
Clomiphene Citrate (Clomid or Serophene)
- Medication used to treat infertility
- Anti-oestrogen medication
• First five days of menstrual cycle
• 70% ovulation rate
• 30% conceive within 3 months
- Taken with metformin if ovulation doesn’t occur
What are the indications for performing Ovarian Drilling?
Indications for performing Ovarian Drilling:
- Women who fail to ovulate when taking ovulation inducing medications
- Women with high LH levels
- Women who do not ovulate and are undergoing laparoscopy for tubal evaluation
What treatments are there for hirsutism?
Hirsutism treatments:
- Hair removal
- Medications: Spironolactone (Aldactone)
Or prescription topical cream
Spironolactone (Aldactone)
Spironolactone (Aldactone)
• Blocks androgen effects
• Reduces androgen production
• Problems:
Diuretic
Heartburn
Headache
Fatigue
What are the different treatments for PCOS?
PCOS treatments:
Oral Contraceptives
Diabetes Medication
Hirsutism Medication
IVF
Surgery Laparoscopic Ovarian Drilling
What are the influencing factors in the development of PCOS?
Influencing factors in the development of PCOS:
- Hyperandrogenism
- Chronic anovulation
- Insulin resistance
- Lipid metabolism disorder
- Chronic inflammation
- Autoimmune response
- Abnormal gut microglora
- Oxidative stress
Why does PCOS have increased CVD risk?
PCOS has increased CVD risk because:
- It is characterised by endothelial dysfunction and resistance to vasodilating action of insulin
- Low grade chronic inflammation contributes
- Hyperandrogenism promotes visceral obesity> hypertension, lower adiponectin levels, incereased leptin
- Insulin resistance promotes dyslipidaemia and T2D
What does hyperinsulinaemia do?
Hyperinsulinaemia:
* stimulates theca cells of ovary to
produce testosterone, exacerbates LH hypersecretion and
lowers the production of sex hormone-binding globulin (SHBG)
in the liver, thereby further increasing hyperandrogenaemia.
What is sex hormone binding globulin?
Sex hormone binding globulin:
- transports androgens and estrogens in blood and regulates their access to target tissues
- low levels of sex hormone binding globulin can be related to high testosterone levels
What is the average length of the menstrual cycle?
The average length of the menstrual cycle is 28 days +/- 4 days.
III Luteal Phase
Pituitary hormone effects:
LH stimulates growth of a corpus luteum from follicular tissue left behind after ovulation (mature egg release).
Ovarian hormone effects:
The corpus luteum secretes oestradiol and progesterone that:
* Block GnRH production by the hypothalamus and LH and FSH production by the pituitary.
* Cause the endometrium to further develop.
If implantation occurs which hormone is released that is important for pregnancy?
hCG - Human chorionic gonadotropin
* secreted if implantation occurs
* important for pregnancy
* used to test if woman is pregnant in early stages
* concentrations diminish throughout pregnancy
Progesterone
Progesterone
Source: Corpus luteum
Functions: * Steroid hormone * Helps in the growth of the
endometrium * Promotes implantation * Support pregnancy
High levels:
* Irregular periods * Lower sexual activities
Low levels:
* Perimenopause (menopausal transition) * Unable to carry the pregnancy
Testosterone
Testosterone
Source: Interstitial cells
Functions: * Male sex hormone * Stimulates the synthesis
of sperm cells * Regulate functions of male sex hormone * Helps in the metabolism
High levels:
* Changes in testicles
* PCOS in women
* Lowering of sperm
Low levels:
* Decrease in activities secondary sex characteristics
* Depression
* Loss in sexuality
Oestrogen
Oestrogen
Source: Ovarian follicles
Functions: * Female sex hormone * Regulate functions of
female reproductive system * Development of the
mammary gland * Helps in milk secretion
High levels:
* Gynecomastia (breast growth in males)
* Irregular menstrual cycle * Depression * Overweight
* Endometriosis
Low levels:
* Irregular periods
* Earlier menopause
* Osteoporosis
