W13 Sex hormone responsive conditions (RT) Flashcards
from Rang and Dale's Pharmacology 10th ed
What are the reproductive or sex hormones (sometimes called sex steroids)?
3 classes?
Oestrogens, Androgens, Progestogens
Oestrogen, Progestrogen, Testosterone
How are sex hormones / sex steroids (and reproductive systems) controlled?
HPG axis
Hormonal control: sex steroids from gonads, mediators from hypothalamus (including GnRH) and gonadotrophin from anterior pituitary
Pituitary Releases:
*FSH (follicular stimulating
hormone)
*LH (Lutenising hormone)
Neurohormonal control of the Female Reproductive System
- HPG Axis
- GnRH controls the secretion of FSH and LH
- FSH and LH - act on the ovaries to promote
development follicles which contains an ovum - Negative feedback
-Oestrogen: anterior pituitary
-Progesterone: anterior pituitary & Hypothalamus
follicle develops into grafian follicle which contains the ovum (egg cell), this releases oestrogen, ovum is released during ovulation and becomes a corpus luteum which produces progesterone
Hormonal control of the female reproductive cycle:
Menses:
* Superficial layer of endometrium shed
Follicular phase:
* Endometrium regenerates
* Proliferative phase of endometrium
* Thicker & more vascular
* Oestrogens
* Developing graffian follicle (contains ovum)
Luteal phase:
* Secretary phase of endometrium- implantation
* Progesterone- Corpus luteum
Hormonal control of the female reproductive
cycle
- 0-14 (menses and follicular phase):
- FSH and LH levels rise slowly
- Promotes ovarian follicle maturation (FSH) (many begin to develop, one forms graffian f. and others degenerate)
- → oestrogen secretion
- Endometrial build up and cervical mucus secretion (sperm survival)
- Oestrogen initially (chronic levels) inhibits FSH/LH
- Oestrogen surge stimulates surge in LH (C)
- INC LH Leads to ovulation:
- corpus luteum formation and progesterone secretion.
- 16-28 Luteal phase: Secretary phase
- Readiness for implantation
-Cervical mucus more viscous less alkaline more hostile
environment for sperm - Progesterone also exerts a negative feedback effect on gonadotrophin (FSH and LH)
- If no fertilisation : Corpus luteum degenerates
- No longer enough progesterone to maintain endometrium
- Repeat of cycle
- (Rise FSH/LH → follicle development
Roles of Sex Hormones:
Whatis the role of Oestrogen?
Synthesised by the ovary and placenta,
* small amounts by the testis and adrenal cortex
Oestrogen binds to ER receptors
* ERα and Erβ
* subsequent genomic effects
- Induces secondary sexual characteristics of female
- Regulates events in menstrual cycle (growth of endometrium)
- Inhibits bone resorption
- Offers protective effect on cardiovascular system
Oestrogens
Pharmacological (exogenous) effect in female?
Types of preparations?
Dependant on sexual maturity
Before puberty: stimulate development
of secondary sexual characteristics
* Adult female: given cyclically (with
progesterone) induces an artificial
menstrual cycle and contraception
* At or after menopause: prevents
menopausal symptoms and protect
against osteoporosis (?)
* Increase coagulation - Increased risk of
thromboembolism??? (see next lecture)
Many preparations:
Oral, transdermal, implantable etc
-Natural: eg oestradiol, oestriol
-Synthetic: e.g. mestranol, ethinylestradiol,
Natural and synthetic oestrogens are well
absorbed in the gastrointestinal (GI) tract, skin
* Metabolised in the liver
-Natural particularly rapidly
-Excreted in the urine as glucuronides
Some unwanted effects
-Oestrogen causes endometrial hyperplasia unless
given cyclically with a progestogen (excess growth of endometrium)
Progestogens
- Progesterone (natural):
- Secreted by the corpus luteum
- by the placenta during pregnancy.
- Small amounts are also secreted
by the testis and adrenal cortex - binds to nuclear receptors
- Responsible for secretory changes in endometrium in
preparation for pregnancy (e.g. thick cervical mucus) - Oestrogens induces synthesis of progesterone receptors
- Progesterone: decreases oestrogen receptor expression
- Progesterone: pre-systemic hepatic metabolism inactive orally
- Derivatives : desogestrel
Progestogens
Main therapeutics?
- Oral contraception
-Often combined with oestrogens: Combined pill
-Progestogen only pill - Used with oestrogen replacement regimens
-Intact uterus, to prevent endometrial hyperplasia and carcinoma - Antiprogestogen – mifepristone
-medical termination of early pregnancy
Oral contraception
what are the types?
Combined Pill
* Oestrogen
* Inhibits FHS
* Inhibits follicle development
Progesterone
* Inhibits LH
* Inhibit ovulation
* Cervical mucus hostile for sperm
* Endometrium unsuitable for
implantation
* May also affect motility of cervix,
uterus and oviducts
Progesterone Only
* Mainly due to changes in cervical mucus
* Hinders implantation –endometrium
-Changes on motility of oviduct
Usually combination is more effective
Menopausal Symptoms include:
Vasomotor Symptoms? (3)
Physical effects? (5)
- Hot flushes / flashes
- Sleep disturbances /night sweats
- Sweat gland opening
▪ Tiredness
▪ Headaches
▪ Joint pain
▪ Vaginal dryness
▪ Urinary frequency / nocturia
(predominantly related to the effect of oestrogen)
Endocrine changes during the menopausal
transition:
- Irregular menstrual cycles
- Onset of symptoms
- Rise in FSH
- Hypothalamic-pituitary axis: lose sensitivity to both positive and negative feedback by oestrogen
- Endocrinology complex: circulating serum levels of oestradiol, FSH, LH fluctuate widely
-Anovulatory cycles
Physiology:
Reproductive cycles
- Primordial follicles grow into mature follicles
- Ovulation
Transition
* Few primordial follicles remain to be stimulated by
FSH and LH
* Production of oestrogens by the ovaries decreases
as the number of primordial follicle reduce
* Oestrogen production falls below a critical value -
the oestrogens can no longer inhibit the
production of FSH and LH
* Increased levels of particularly FSH
* Atretic follicles – low levels of oestrogen
Physiology
Irregular cycles:
- Anovulatory cycles
- Endometrium has proliferated under oestrogen
- No ovulation
- No Corpus luteum
- Lack of progesterone
- Endometrial lining breaks down
-irregular - Reduce as oestrogen decreases
Physiology
Oestrogen receptors (ER) found in CNS
Vasomotor Changes
* (heat dissipating events)
* Peripheral vasodilation
* Transient rise in body temperature
* Hot flash: acute sensation of heat
* Flush – vasomotor episode:
* Perception, skin changes, excessive sweating (diaphoresis)
Cause still unclear
* lower oestrogen and higher FSH (LH) levels
* Thermoregulatory centre in hypothalamus
* Heat dissipations/ reduction in core temp
