Drugs affecting reproductive function Flashcards
Oestrogens - where secreted from and what is principal oestrogen?
Synthesised by ovary and placenta and in small amounts in adrenal cortex and testis
There are three main endogenous oestrogen in humans:
Oestradiol is the most potent and principal oestrogen secreted by the ovary
Oestrogen mechanism
Interaction with nuclear receptors to regulate gene transcription
Some oestrogen effects (rapid vascular actions) are initiated by interaction with membrane receptors
Effects of oestrogen depend on state of sexual maturity
In primary hypogonadism oestrogens stimulate development of secondary sexual characteristics and accelerate growth
In adults with amenorrhoea they are given cyclically with progestogen, they induce an artificial menstrual cycle
Prevent menopausal symptoms and protect against bone loss but increase coagulability of blood and inc risk of thromboembolism
Therapeutic uses of oestrogens
Replacement therapy in primary ovarian failure (Turner syndrome) to promote sexual maturation
Replacement therapy for menopausal symptoms such as flushing, vag dryness and osteoporosis
In contraception they are used singly or in combination with progestogens, prostate and breast cancer
When admin to males they cause feminisation
Oestrogen preps
Oral, TD, IM, implantable and topical
Well absorbed from gut, across skin and mucous membranes
They include natural (estradiol, estriol) and synthetic (mestranol, ethinylestradiol) oestrogens
In the blood they are bound to albumin and to a sex hormone binding globulin
Unwanted effects include breast tenderness, N&V, anorexia, salt and water retention with oedema and inc TE risk
SERMs - selective oestrogen receptor modulators
Tamoxifen used in oestrogen dependent breast cancer (antagonist in breast but agents in uterus)
Raloxifene to treat post-menopausal osteoporosis
Clomiphene is a pure oestrogen antagonist at hypothalamus and pituitary
Progestogens
Secreted by corpus luteum late in menstrual cycle and by placenta during pregnancy
Acts on prog receptor to regulate gene transcription target tissues
Oestrogen stimulates synthesis of PR and progesterone inhibits synthesis of oestrogen receptors
Progesterone not used therapeutically due to rapid clearance but synthetic derivatives are used (progestins)
Derivative of natural progesterone include medroxyprogesterone and hydroxyprogesterone
Also testosterone derivatives - norethisterone, desogestrel, gestodene
Therapeutic uses of progesterones
Oral contraception (alone/with oestrogen) Used as progesterone only injectable or implantable contraception or part of intrauterine contraceptive Combined with oestrogen for oestrogen replacement therapy in women with an intact uterus to prevent endometrial hyperplasia, carcinoma, endometriosis
Adverse effects of progestogens and use of anti-progestogens
Acne, fluid retention, weight gain, depression, change in libido, breast discomfort, menstrual cycle irregularity and increased TE
Mifepristone in combination with progesterone analogues is an effective medical alternative to surgical termination of early pregnancy (up to 9w)
Combined pill - mode of action
Oestrogen inhibits FSH secretion via -ve feedback on ant pituitary and thus suppresses development of ovarian follicle
Progestin inhibits LH secretion and prevents ovulation
Oestrogen and progestin act in concert to alter endometrium in such a way as to discourage implantation
They may also interfere with coordinated contractions of cervix, uterus and fallopian tubes that facilitate fertilisation and implantation
AE’s with combined pill
Mild nausea, flushing, dizziness, bloating
Weight gain, skin changes, (acne/pigmentation), depression or irritability
Amenorrhoea of variable duration after cessation of pill
Serious withdrawal effects are rare
A small number of women develop reversible HTN, small increase in risk of TE
Other regimens for contraception (apart from oestrogen and progesterone)
EHC - levonorgestrel
Long acting progestogen only contraception - medroxyprogesterone, levonorgestrel
Post-menopausal HRT
At menopause ovarian function decreases and oestrogen levels fall - can be treated with HRT - cyclic or continuous admin of low dose oestrogens (estradiol, estriol) with or without progestogens
Improves symptoms caused by reduces oestrogen such as hot flushes and vaginal dryness, prevents and treats osteoporosis
Drawbacks include withdrawal bleeding, inc breast cancer risk, endometrial cancer risk, inc risk of thromboembolism
Androgens
Testosterone is main androgen
Synthesised by Leydig cells in testes and in smaller amounts in adrenals and ovaries
GnRH acts on anterior pituitary to release both FSH and LH
LH stimulates androgen secretion
IM depot injections or patches of testosterone esters are used for replacement therapy in male hypogonadism due to pituitary or testicular disease and female hypo sexuality following ovariectomy
Mechanism of action is via nuclear receptors and control of gene expression
Effects depend on age/sex and include development of male secondary sex characteristics in pre-pubertal men and masculinisation of women
Antiandrogens (flutamide, cyprotenue) are used as part of tx of prostatic cancer
Dihydrotestosterone synthesis inhibitors such as finasteride are used in BPH
Anabolic steroids
Androgens can be modified to alter anabolic and other effects - nandrolene increases protein synthesis and muscle development
Used in therapy of aplastic anaemia, abused by some athletes
Yes can include infertility, salt and water retention, CHD and liver disease
Gonadotrophin releasing hormone analogues
GnRH is a decapeptide - analogues are used to manipulate the reproductive axis
Gonadorelin is the same AA sequence as endogenous form but made synthetically
Nafarelin is a more potent analogue
Given in pulsatile fashion will stimulate release of FSH and LH and induce ovulation, used in infertility tx
Admin of GnRH in a continuous regimen will induce gonadal suppression - used in sex hormone dependent conditions (prostate and breast cancers, endometriosis and large uterine fibroids)
