Male sex hormones

Male sex hormones
Presentation lecture by:By C.Adithan

Male sex hormones
Androgens
* Synthesis& secretion
* Regulation
* Pharmacological actions
* Pharmacokinetics
* Preparations
* Therapeutic uses
* Adverse effects

Anabolic steroids
* Differ from androgens?
* Preparations
* Therapeutic uses
* Adverse effects

Anti-androgens
* Danazole
* Cyproterone acetate
* Flutamide
* Finasteride

Androgens
* Includes testosterone, DHT & androstenedione
- Testosterone serves as a prohormone for
o Dihydrotestosterone (DHT)
o Oestradiol

Cholesterol
Pregnenolone
Progesterone
17-α- Hydroxy pregnenolone
17- Hydroxy progesterone
Dehydro-epi androsterone
Andro-stenedione
Oestrone
Oestriol
TESTOSTERONE
OESTRADIOL

Regulation of secretion
* Oestrogen – similar to Testosterone
* Inhibin inhibits FSH secretion at A.P level

Testosterone & DHT
+ growth of genitals in a boy
+ production of sperm
+ growth of facial, pubic & axillary hairs
+ muscular development
+ growth of larynx & voice deepens
+ inhibition of bone growth
+ thickening of skin, loss of s.c. fat
+ behavioral changes in men
+ nitrogen retaining effect
+ erythropoietin secretion increased
+ Increased LDL & decreased HDL

Transdermal patches
Orally active preparations:
* Methyl testosterone tab.
* Fluoxymesterone
* Mesterolone

wall of abdomen/thigh
Implants
Testosterone esters:

* Testo. propionate
* Testo. phenylpropionate
* Testo. cypionate
* Testo. enanthoate

Testosterone aq. suspension
Pharmacokinetics
Clinical uses of testosterone
* Testicular failure: Primary & Secondary
* Chronic illness
* Burns
* Osteoporosis
* Long term corticosteroid therapy
* Pituitary dwarfism
* Carcinoma of breast
* Hereditary angioneurotic oedema
* Anaemia (refractory)
* Menopausal syndrome

Adverse effects of testosterone
* Virilization (female)
* Feminizing side effects (male)
* Precocious puberty & stunted growth
* Cholestatic jaundice
* Enlargement of prostate
* Atherosclerosis
* Hepatic carcinoma
* Oedema

Anabolic steroids
Uses of anabolic steroids
o Osteoporosis
o Catabolic states
o Short stature
o Anaemia (refractory)
o Athletic performance

Anti-androgens
* Danazol
* Cyproterone acetate
* Flutamide
* Finasteride

Side effects:
Dose related
Amenorrhea (High doses)
Androgenic side effects
Uses:
* Endometriosis
* Menorrhagia
* Fibrocystic breast disease
* Hereditary angioneurotic
* Gynecomastia
* Infertility

* FSH & LH release in both sexes
* Binding of steroids to receptors
* Enzymes needed for steroid synthesis
* Weak androgenic, anabolic, progestational & glucocorticoid action

Cyproterone acetate
* Block androgen receptors
* secretion of gonadotropins
Uses:
* Acne
* Male pattern of baldness
* hirusitism
* Ca. of prostate
* Virilizing syndrome
* Precocious puberty
* Inappropriate behaviour

Flutamide
* Non-steroidal anti-inflammatory
* Antagonise androgens:
o Accessory sex organs
o Pituitary

Uses:
* Cancer of prostate along with GnRH agonist
* Female hirusitism
Prostate volume
Symptom score
Peak urine flow rate
DHT level in prostate
Side effects: Loss of libido & impotence in 5 % pts.
Also used for prevention of hair loss

Male sex hormones.ppt

Read more...

Puberty

Puberty
Presentation by:Angela Bauer-Dantoin, Ph.D.
Associate Professor, Human Biology and Women's Studies
University of Wisconsin Green Bay

* defined as transition period between sexually immature child to sexually mature, fertile adult
* involves growth and maturation of many tissues
* timing has much individual variability
* sequence of events doesn’t vary
* timing differs between the sexes:
o growth spurt begins ~2 yrs earlier in females
o females become fertile ~1 yr earlier than males

Typical sequence of pubertal events Females vs. Males
Ovarian changes during childhood
Testicular changes during childhood
* at birth, seminiferous tubules contain only Sertoli cells and spermatogonia
* Leydig cells are present at birth; disappear by 6 months of age
* Leydig cells reappear at 9-10 yrs. > spermatogenesis begins
* mature sperm not produced until 14-15th yr.
* spermatogenesis depends on descent of testes into scrotum
* body temperature prevents spermatogenesis
* descent >months 7-9 of gestation
* under influence of testosterone
* testes “guided” by gubernaculum (cord attached to testes, scrotum)

Cryptorchidism
* in 3-4% of newborn males, testes haven’t descended
* consequences:
o germ cells killed by normal body temperature
o increased incidence of testicular cancer
* usually corrected with surgery or gonadotropins / GnRH by 2 yrs

Hormonal changes at puberty
* in young children, LH and FSH levels insufficient to initiate gonadal function
* between 9-12 yrs., blood levels of LH, FSH increase
* amplitude of pulses increases, especially during sleep
* high levels of LH, FSH initiate gonadal development
* GH secretion from pituitary also increases
* TSH (thyroid stimulating hormone) secretion from pituitary increases in both sexes:
o increases metabolic rate
o promotes tissue growth

Female hormonal changes
* surge of LH release initiates 1st ovarian cycle
* usually not sufficient to cause ovulation during 1st cycle
* brain and endocrine systems mature soon thereafter
* estrogen levels in blood increase, due to growing follicles
* estrogen induces secondary sex characteristics:
o growth of pelvis
o deposit of subcutaneous fat
o growth of internal reprod. organs, external genitalia
* androgen release by adrenal glands increases > growth of pubic hair, lowering of voice, growth of bone, increased secretion from sebaceous glands

Male hormonal changes
* LH and FSH release increases ~10 yrs. of age
* spermatogenesis; androgen secretion
* adrenals also secrete androgens
* androgens initiate growth of sex accessory structures (e.g. prostate), male secondary sex characteristics (facial hair, growth of larynx)
* androgens causes retention of minerals in body to support bone and muscle growth
* Sertoli cells also secrete some estrogen

Gonadostat hypothesis

* “Prepubertally, steroid hormone feedback operates at a very low setpoint; at puberty, set point increases.”
* if setpoint is raised at puberty, then LH and FSH levels would increase
* evidence: smaller amount of estrogen needed to lower gonadotropin levels in children (vs. adult women)
* evidence against hypothesis: in children without gonads, increase in LH, FSH levels occurs at normal age
* conclusion: even though puberty involves a change in setpoint, it is not the driving force for puberty

Hypothalamic Maturation Hypothesis

* “Activation of reproductive system at puberty is due to maturation of hypothalamus”.
* assume GnRH is driving force for puberty
* supporting evidence:
* in monkeys and humans, secretion of GnRH increases at puberty in absence of gonads
* give immature monkey GnRH > will show ovulatory cycles with estrogen, LH surges
* females with Turner’s Syndrome (XO) show normal LH, FSH onset
* tumors secreting GnRH can cause precocious puberty

Timing of puberty
* trend toward earlier puberty exists within W.
Europe and USA
* examination of lifestyle changes may give clues regarding mechanisms inducing onset
* 2 possible contributing factors: photoperiod and nutrition

Photoperiod
* refers to daylength (amount of light to which a person is exposed / day)
* electricity allows us to artificially extend daylength
* typically, we see only 8 hrs of darkness / day
* simulates summer photoperiod (“long days”)
* evidence against photoperiod hypothesis:
o intensity of domestic light not sufficient to affect neural mechanisms regulating GnRH secretion
o little evidence that photoperiod regulates human reproductive activity
Nutrition

* “Critical body weight must be attained before activation of the reproductive system”.
* even though age of menarche is decreasing, the average body weight of menarche remains the same
* earlier puberty due to improvement of nutrition, living conditions, healthcare?
* evidence supporting hypothesis:
o obese girls go through early menarche
o malnutrition is associated with delayed menarche
o primary amenorrhea common in lean female athletes
o “bodyfat” setpoint very noticeable in girls with fluctuating body weight due to anorexia nervosa

Puberty.ppt

Read more...

Puberty

Puberty
Presentation lecture by:Dr. Penny Frohlich
Hormones & Puberty

* Hypothalamus stimulates pituitary gland
o growth hormone which causes growth spurt
o ovaries and testes release gonadotrophins (sex hormones)
+ males: testosterone
+ females: estrogen and progesterone

Hormones & Puberty
* hormones stimulate
o growth of primary sexual characteristics (genital)
o growth of secondary sexual characteristics (non-genital)
o precursors to adult sexuality

Sex Differences in Puberty

* Growth spurt begins
o 10.5 years in girls
o 12.5 years in boys
o girls taller than boys between ages 11-13 years
* full adult height
o 17 years old in girls
o 21 years old in boys

Sex Differences in Puberty
* Menarche: first menstrual cycle
o typically occurs by age 12-13
o initially may involve anovulatory, irregular cycles
* Spermarche: first ejaculation
o typically occurs by age 15
o initial period of sterility

Sex Differences in Puberty
* Puberty marks an increased incidence of internalizing disorders in girls compared to boys (Haward & Sanborn, 2002; Kessler, 2003)
* Due to hormones? Environmental variables? Pregnancy?
* Is depression adaptive? (Nesse, 2000)

Precocious and Delayed Puberty
* Girls who enter puberty early more likely to have teen pregnancy
* girls who have teen pregnancy, more likely to have daughters with teen pregnancy

Precocious and Delayed Puberty
* Vandenbergh Effect
o male present --> earlier onset of puberty
o females only --> later onset of puberty
o may be a way of regulating population density

Precocious and Delayed Puberty
* Stable species – unchanging predictable environments, live long lives in large populations, large bodied, lavish lots of parental attention on few offspring – reach puberty later
* Opportunistic species – unstable unpredictable ecosystems – conditions good, everyone begins mating or pollinating --> conditions favorable, reach puberty rapidly

Precocious and Delayed Puberty
* Absent Father Theory:
o girls abandoned by their father behave like females from opportunistic species and reach puberty earlier (Draper, Belsky, & Harpending).
o process may be caused by pheromones
* Strategies for reproductive success
1) early pubertal development, low investment in offspring
2) later pubertal development, high investment in offspring
* Evidence in support:
o females with absent father reached puberty earlier (Surbey, 1988, 1990)
o females with greater emotional distance from parents reached puberty earlier (Sternberg, 1988)
o females with greater stress in parental relationship reached puberty earlier
Correlation does not equal causation!!!
* Absent father predicts early puberty:
o stress tends to delay menarche
o postpuberty stress inhibits ovulation
* Absent father predicts early puberty
o absent father may lead to lower SES
o lower SES may lead to problems associated with early menarche
* Absent father predicts early puberty
o Wamala et al. (1997)
+ 300 Swedish women ages 30-65
+ examined reproductive history, weight, SES
+ Findings: SES and obesity associated with higher number of children and earlier menarche
* Absent father predicts early puberty
o when the father is absent, mother may have poorer prenatal care (diet, rest, etc)
o Koziel & Jankowska (2002)
+ 1060 Polish girls aged 13.5 to 14.5 years
+ collected BMI and weight data
+ Findings: BMI and birthweight affected onset of menarche

* Early puberty predicts absent father:
o Mother’s genetics predicts earlier puberty
o Girls with early puberty get attention from males earlier - more likely to get pregnant?
o Girls likely to inherit onset of puberty from mother
* Third variable predicts absent father and early puberty:
o variant of x-linked androgen receptor that:
+ predisposes father to unstable relationships
+ causes early puberty in female offspring who inherit
o Comings et al. (2002): significant association between this gene and the following characteristics:
+ aggression and impulsivity
+ increased number of sexual partners
+ sexual compulsivity
+ paternal divorce
+ father absence
+ early menarche in females

* Early puberty, early spermarche

Hormones & Puberty.ppt

Read more...