W10 - PUBERTY AND MENOPAUSE Flashcards
Define puberty. Explain the process of the attainment of fertility in males and females
- Puberty is defined as the ability to successfully reproduce
- Achievement of fertility
- Puberty is a process that takes time, not a single event
- Derived from the Latin pubscere which means “to be covered with hair”
- Hair-growth around genitals, armpits and legs
- Attainment of fertility has many definitions in females
- Age of menarche - the first menstrual period
- Definitive sign of onset of puberty - higher oestrogen levels in order to stimulate proliferation of endometrium and removal for shedding
- Menarche does not mean first ovulation (months to two years later)
- First few - low FSH and LH levels so follicles do not mature fully, but still produce enough oestrogen to build up endometrium and then low levels for shedding
- Age of first ovulation
- Difficult to observe (does not mean fertility)
- Requires microscopic surgery, ultrasound, monitoring in order to tell
- Still not indicative that an individual would be able to carry a pregnancy to term - not right ratio of progesterone and oestrogen to maintain a pregnancy
- Difficult to observe (does not mean fertility)
- Age of dependable ovulation in which a female can support pregnancy without deleterious effects
- Metabolic costs of pregnancy and lactation are high
- Depends on reaching a threshold body size and condition
- Age of menarche - the first menstrual period
- Attainment of fertility has many definitions in males
- Age of first ejaculation
- Definitive sign of onset of puberty
- Ejaculation does not mean successful fertilisation (early ejaculate often azoospermic)
- Seminal vesicle secretion - accessory glands are being stimulated by testosterone
- Age when spermatozoa first appear in ejaculate
- First sperm does not mean successful fertilisation (sperm-containing ejaculates initially oligozoospermic)
- Age when ejaculate contains threshold number of spermatozoa - successful natural fertilisation
- <15 million/mL is sub-fertile
- 10-14 for boys (Onset) - first indication of puberty
- Enlargement of testes and scrotum
- Age of first ejaculation
Explain the changes in the hypothalamic-pituitary-gonadal axis during the onset of puberty
- The onset of puberty is regulated by the hypothalamus
- Depends on hypothalamic neurons producing sufficient quantities of GnRH to promote and support gametogenesis
- Hypothalamus functionally different in males and females (absence of positive feedback in males)
Explain the significance of alpha-fetoprotein and the blood-brain barrier
- Hypothalamus is inherently female
- Males
- Testosterone from foetal testis “defeminizes” the brain by inhibiting the surge centre
- It Is oddly oestradiol that is responsible for this process
- Females
- Alpha-fetoprotein in foetus prevents oestradiol from crossing the blood-brain barrier
- No internal oestradiol = Surge centre (hypothalamus) develops
Explain the changes in GnRH secretion before and after puberty
- Before puberty
- Males and females - pulses of low frequency and amplitude (tonic centre)
- After puberty
- Males and females - pulses of increased frequency and level (tonic)
- Females only - with preovulatory burst (surge centre)
Explain why LH secretion differs between males and females
- Males
- LH secretion in men is of low amplitude with regular pulses (every 2-6 hours)
- Females
- There is a surge every cycle separated by low amplitude pulses
Explain the function of testosterone
- Responsible for spermatogenesis and characteristics that define the masculine body
- Production increases rapidly during puberty to decrease responsiveness of the hypothalamus-pituitary axis to negative feedback
- Starts the development of sexual characteristics
- Development of male primary sexual characteristics
- Penis, scrotum and testes increase in size (8-fold increase by 20 years)
- Prostate gland
- Seminal vesicle
- Male genital ducts (Including epididymis and vas deferens)
- Development of male secondary sexual characteristics
- Body hair - over abdomen, face and chest
- Baldness - decrease growth of hair on top of head
- Voice - hypertrophy of laryngeal mucosa and enlargement of larynx
- Skin - increased thickness, increased sebaceous gland secretions and acne
- Muscles - protein formation and muscle development
- Bone - increase bone matrix and Ca++ retention
- Metabolism - increase basal metabolism
- Behaviour - promotes sex drive (libido) and aggressiveness
- Development of male primary sexual characteristics
Explain the functions of oestrogen
- Responsible for the onset of ovarian and uterine cycles (triggers ovulation and endometrial proliferation) as well as characteristics that define the feminine body
- Production increases 20-fold during puberty due to decreased responsiveness to the hypothalamic-pituitary axis to negative feedback
- Stimulates the development of sexual characteristics
- Development of female primary sexual characteristics
- Vagina, uterus, oviducts and external genitalia enlarge
- Uterus and oviducts exhibit enhanced motility
- Vaginal mucosa thickens
- Stimulates “watery” cervical mucus (facilitates sperm transport)
- Development of female secondary sexual characteristics
- Breasts - development of stroma and duct system
- Bone - promote long bone growth, widening of pelvis, Ca++ retention and eventual epiphyseal closure
- Fat - deposition of subcutaneous fat (breast and hips)
- Metabolism - increased HDL (high-density lipoproteins) and decreased LDL (low-density lipoproteins) in blood
- Skin - increased hydration (soft and smooth texture)
- Development of female primary sexual characteristics
How do GnRH neurons acquire the ability to release GnRH in high frequency pulses?
- Onset of puberty is not limited by gonads or anterior pituitary
- Exogenous pulsatile GnRH treatment in prepubertal primates causes LH and FSH release
- Exogenous FSH and LH treatment causes follicles to grow and produce oestrogens in prepubertal ovaries
- Puberty depends on the release of sufficient quantities of GnRH from the hypothalamus
- This process occurs gradually
- Before puberty
- Tonic centre is highly sensitive to negative feedback by low levels of oestrogens and testosterone from the ovaries or testes of females and males respectively
- The surge centre is not yet responsive to positive feedback by oestrogen
- During pubertal transition
- Sensitivity begins to decline and increasing amounts of GnRH are produced by the tonic centre
- Need more oestrogen and testosterone to suppress GnRH until a new equilibrium is established
What causes the tonic centre to lose sensitivity to negative feedback?
- Pregnancy and lactation exert a high metabolic cost
- A certain degree of fat reserves are needed before the brain “allocates” energy to initiate reproductive processes
- However, “fatness” alone does not promote puberty
- Young girls can be obese but not peripubertal
- Also depends on reaching a threshold body size/condition
- Fatness and the underlying metabolic signals are best understood in the female
- The loss of sensitivity and initiation of high frequency GnRH pulses may be influenced by concentration of glucose, leptin or fatty acids in blood
- Possible influence of metabolic signals on GnRH neurons
- Blood glucose levels (another indicator of metabolic status) might stimulate glucose sensing neurons that in turn stimulate GnRH neurons
- Adipocytes produce leptin that enter the blood - may stimulate neuropeptide Y neurons or directly stimulate GnRH neurons
- Blood leptin reflects nutritional status because the greater amount of fat, the greater the amount of leptin
Explain the trend towards earlier onset of puberty in girls
- Related to improved quality and quantity of food but critical weight (approximately 47kg) must be obtained
What is menopause?
- The permanent cessation of menstruation that results from the loss of ovarian follicular function
- Diagnosed retrospectively after 12 months amenorrhea
- Functionally equivalent to oestrogen withdrawal syndrome
- From the Greek
- “Meno” means month
- “Pause” means cessation/stop
- Menopause is a natural stage in a woman’s life
Explain the physiology of menopause
- Loss of ovarian responsiveness to gonadotrophins due to decline in follicles
- Ovarian oestrogen, inhibin and progesterone production falls
- Serum FSH and LH levels slowly rise
- Menstrual cycle length is variable then decreases as follicular phase shortens
- Ultimately ovulation and menstruation cease entirely
- Postmenopausal ovary is small and devoid of follicles
Explain the timing of menopause
- Average age
- 51 years
- Normal range
- 45 to 55 years
- Genetically determined
- Maternal menopausal age predicts age in daughter
- Smokers enter menopause earlier
- Preceded by climacteric or perimenopause (Reproductive transition period)
- Generally evident mid-late 40s (as early as 35)
- Lasts several years, 10 years, or longer
What are some symptoms and concerns associated with the menopausal transition?
- Menstrual irregularities
- Cycle length varies, shortens then stops
- Hot flushes (75%)
- Sudden intense feelings of heat and profuse sweating, night sweats (may last 1 to 5 years)
- Mood disturbances
- Headaches, irritability, insomnia, depression
- Atrophy of reproductive tract and breasts
- Decrease in size and internal secretions (vagina more prone to infections and pain during intercourse)
- Urinary frequency, urgency and incontinence
- Bone changes
- Increased bone resorption and diminished formation results in thin fragile bones
- Cardiovascular changes
- Increase in low density lipoprotein (LDL), decrease in high density lipoprotein (HDL) and weight gain
- Concerns
- Increased risk of cardiovascular disease
- Increase risk of osteoporosis
- 50% vertebrae and 25% hip fractures by age 80
What are some underlying causes of menopause?
- Menopause = Oestrogen withdrawal syndrome
- Developing follicles are a source of ovarian oestrogens
- Primary cause - depletion of finite pool of follicles