PROGESTINS

AND
ANTIPROGESTINS

1
 Learning Objectives

At the end of the lecture , students

should be able to-
Enlist the available synthetic
Progestins
Describe the mechanism of action of
Progestin, pharmacological cations and its
side effects

Describe the mechanism of action and

clinical indications of AntiProgestins
 NATURAL PROGESTERONE
Introduction

 Progesterone (21 carbon steroid) is derived from

cholesterol
 It was first isolated in 1929
 Males also produce 1-5mg progesterone per day from
adrenals and testes [but role in males is not known]
 Progestins
NATURAL PROGESTERONE

Converts the estrogen primed proliferative endometrium to secretory and maintain pregnancy in animals spayed after
conception

●
Progesterone
●
Secreted form corpus luteum post-ovulation and immediately after fertilization (corpus luteum sustained by
chorionic gonadotrophins released by blastocyst); from placenta during 2nd and 3rd trimester; from adrenals

Natural Progestin:
 Progestin preparations

Progesterone Newer
analogues 19-Nortesterone 19-Nortesterone
derivatives derivatives
Hydroxy progesterone Norethisterone Desogestel*
Medroxy progesterone Norethynodrel Norgestimate*
Megesterol acetate Ethinylesterol Gestodene
Dihydrogesterone Norgestrel
Nomegestrol* Levonorgestrel* Potent & pure progestins
No androgenic
Strong Antiovulatory
Progestogenic , Anabolic activity
Pure progestins Weak androgenic & estrogenic
Weak androgenic & Potent Antiovulatory
Antiovulatory activity Don't antagonise the
Along with oestrogen beneficial effects of E.
HRT in P.M.W Contraceptives along
Threatened abortion with estrogens.
Contraceptive along
Endometriosis- for Lipid friendly.
with estrogens
selective p effect Rx of hyperandrogemia.
PHARMACODYNAMICS
PROGESTINS
Bind to nuclear receptors (PR-A and PR-B)

Dimerization & conformational

change in PR

Bind to PREs, recruiting co-

activators

 transcription of target genes

 Progesterone
• Progesterone Receptors:
– Limited distribution: female genital tract, breast, CNS, pituitary
– Nucleus of target cells
– Short (PR-A) and Long (PR-B) isoforms
• Mechanism of Action:
– Binds to Progesterone Receptor (PR) present in nucleus  Undergoes
conformational changes (dimerization)  attaches to Progesterone
Response elements (PRE)  regulates transcription through coactivators
– Cell membrane receptors: rapid effects (Ca++ release from spermatozoa,
Oocyte maturation)
 Progesterone: Pharmacokinetics

Pharmacokinetic Parameters Profile

Absorption • Inactive orally, high first pass metabolism in liver
• Injected intramuscularly as oily preparation
• Micronized formulation for oral administration; absorption
through lymphatics
Distribution • Short half life (5-7 mins)
Metabolism • Converted to Pregnanediol in liver
• Conjugation with glucuronic acid and sulfation

Excretion • Excreted in urine

• Effects lasts longer than the hormone itself

• Synthetic Progestins: orally active, metabolized slowly; longer half life
 USES OF PROGESTINS

Life span of female

Contraception. HRT(adjuvant)
Menarche DUB Menopause Endometrial
Endometriosis carcinoma
Threatened
and habitual
abortion
Postponement
of periods
 PROGESTINS

THERAPEUTIC USES

●
Contraception: alone or in combination with estrogen.
●
MHT
●
Ovarian suppression
●
Dysmenorrhea
●
Endometriosis
●
Dysfunctional uterine bleeding (DUB)
●
Threatened and habitual abortion
●
These agents are used in the treatment of endometrial carcinoma and endometrial hyperplasia.
●
Premenstrual syndrome.
●
These agents are used diagnostically to evaluate endometrial function in amenorrhea.
 SIDE EFFECTS OF PROGESTINS
• Natural(micronized) progesterone
Fatigue
Somnolence
• Synthetic
progestins
Acne
Alopecia Anxiety
Hirsutism Depressio
Hoarse voice n Myalgia
Fluid retention Oedema
Abdominal bloating
 Mifepristone

Blocks Blocks Antiandrogenic &

Decreases the
P.Receptors progesterone Antiglucorticoid
progesterone
support to secretion
endometrium
Contragestational
agent Softens
Endometrial the cervix
x
R Cushing
syndrome
shedding

PG release Favourable
Pregnancy for Abortion
termination
Uterine Sensitises the
contractions myometrium
to P.Gs
Conceptus detached
from uterine wall Facilitates menstruation
 Mifepristone Uses

1. Termination of pregnancy- up to 7wks.

 Mifepristone(600mg,orally) + Misoprostol(400mg
orally) / Gemeprost (1mg as pessary).
 Midterm abortion-(13-24wks)-Mifepristone +
Gemeprost.
 If adm within 10days of missed period results heavy
period.
 Its not effective after 7wks, becoz later placenta starts
enough P to over come the antiprogestin effects of
mifepristone.
2.Postcoital contraceptive-
 Mifepristone -within 72hrs of intercourse, interferes
with implantation.
 Effective method for emergency contraception.

3.Softening cervix-Mifepristone soften & dilates cervix,

prior to surgical abortion/ labour induction.
4.For induction of labour- intrauterine foetal death.
5.Uterine fibroids.
6.Progesterone dependent brain neoplasm.
7.Breast cancer.
8. Cushing's syndrome- as a palliative.
S/E:- abortion failure, prolonged bleeding, abdominal
cramps, vomiting, diarrhoea & anorexia.
D.I- with E.inducers/inhibitors are observed.
Onapristone- newer Antiprogestin & effective.
In which of the following condition progestin is used alone without
combining with an estrogen:
A. Threatened abortion
B. Dysfunctional uterine bleeding
C. Hormone replacement therapy
Mefipristone is a:
a)Aromatase inhibitors
b)Antiprogestin
c)SERM
A breast feeding women was taking oral contraceptives, after few months she noticed
some hair growing on her face and acne, which one of the following drugs would cause
her symptoms?
 A. Norethindrone
 B. Norgestimate
 D. Desogestrel
Which of the following is synthetic Progesterone devoid from systemic androgenic
effect?
 A. Norethindrone
 B. Norgestrel
 C. Medroxyprogesterone acetate
 D. Norgestimate
Which of the following can act as a single dose postcoital contraceptive:
 A. Clomiphene citrate
 B. Ethyinyl estradiol
 C. Norgestimate
 D. Mifepristone
 Mifepristone possesses the following activities:
A. Potent anti-progestin + weak androgenic
B. Potent anti-progestin + weak antiglucocorticoid
C. Potent anti-estrogenic + weak antiprogestin
D. Potent anti-estrogenic + weak glucocorticoid