- Progesterone is a steroid hormone that plays several important roles in the female reproductive system and pregnancy. It can be produced naturally in the body or taken as a synthetic progestin medication. - There are two major progesterone receptor subtypes, PRA and PRB. PRA inhibits the effects of PRB and other steroid receptors in many tissues where they are expressed. - Micronized natural progesterone from plant sources has fewer side effects than older synthetic progestins and more closely mimics the body's endogenous progesterone. It can be administered orally, vaginally, or through other routes. - Progesterone supplementation shows benefits for preventing preterm birth and recurrent pregnancy loss according to some studies,

1. PROGESTERONEPROGESTERONE
New Values In Clinical PracticeNew Values In Clinical Practice
Dr. Mamdouh SabryDr. Mamdouh Sabry
MD. Ain Shams, PhD. FranceMD. Ain Shams, PhD. France
Consultant Ob. & Gyn.Consultant Ob. & Gyn.
EL Mataria Teaching Hospital, Nasser InstituteEL Mataria Teaching Hospital, Nasser Institute
Cairo, EgyptCairo, Egypt

2. Steroid Hormones
• Cholesterol is the basic building block of
steroidogenesis, the placenta synthesize
cholesterol from acetates.
• Steroids are divided into 3 main groups
based on number of carbon atom possessed.
• The 21-carbon series includes corticoids and
progestins, pregnane nucleus is the basic
structure, the 19-carbon series includes all
androgens and based on androstane nucleus
while estrogens are 18-carbon steroids
based on estrane nucleus.
• Prehydrocyclopentanephenanthrene mol. is
the basic structure of steroids with relative
minor chem. diff. leading to great alteration
and minor similarity in biochemical activity.

3. Progesterone
• First discovered in 1929, isolated in 1933 by Willard M.
Allen and George W. Conner, named progestins.
• Progestogens either endogenous or exogenous ( having
progesterone like action).
• Endogenous is formed in corpus luteum, placenta ( week
7-9 ), adrenal cortex and testis.
• Exogenous either synthetic progestins or natural
progesterone, from natural sources after extraction and
synthesis.
• Progesterone receptor ( PR ) is an intra nuclear receptor
having two isoforms, PRA & PRB.
• PR expressed in most systems and organs of the body.

4. Progesterone Receptors
• Two major forms, PRA, PRB receptors.
• PRB is the positive regulator of
progesterone response gene and PRA
inhibits its B activity in most cells of action.
• The repression ( ) of estrogen receptor
transcription activity ( mRNA formation ) as
well as ( gluco., mineralocorticoids and
androgens transcription ) is dep. on PRA
expression, A receptors regulates inhibition
of steroid action wherever expressed.

5. Progesterone receptors (cont.)
• PRA inhibits estrogen receptors only in
cells with critical factor.
• Progesterone shares with estrogen and
(all steroid probably) the ability to exert
activity at the cell membrane
independently of progesterone receptors.
• For example, progesterone or its
metabolite can prevent ut. contractions by
binding to exogenous G protein receptor in
cell membrane inhibiting its function.

6. Classification
Endogenous
(progesterone)
• Secreted by different
body tissues.
• Bound to albumin (50-
54%), cortisol binding
protein (43-48%)
• Metabolised by reduction
or conjugation rabidly by
liver.
• Excreted in urine or bile.
Exogenous
(progesterone like action)
Natural or Synthetic
Natural from nat. sources as
soya beans and Mexican
yam roots, (extr, synth.),
micronized with less side
effects, rapidly absorbed..
Synthetic progestins have
many classifications,
absorbed and rapidly
metabolized, short half
life, given twice or thrice
daily. Not free from side
effects.

7. II. Progestin Content

8. New Progestins
• Include desogestrel, gestodine,
norgestimate and drosperinone. Also,
newer are in development.
• New progestins increase SHBG, decrease
free testosterone ( acne and hirsutism ),
do not affect cholesterol. They may even
improve the lipid profile.
• Families X generations.

10. Function
• Endometrial growth.
• Increase glycogen, mucin & fat in endometrium.
• Suppresses LH.
• Stimulates mammary glands for lactation.
• Has some diuretic effect.
• Decrease maternal immune response during
pregnancy to enhance pregnancy outcome.
• Inhibits premature delivery ( diff. mechanisms ).
• Has anti prostaglandin, anti inflammat. activity.
• Increase epidermal growth factor.
• Body temp., BMR, antispasm.,…….

11. Natural Progestogens( Micronized)
• Develops from natural sources after
extraction and synthesis.
• Plant sources like soya beans and
Mexican Yam roots.
• Rarely from animal ovaries.
• Available in oral, vaginal, rectal or
injectable.

12. Oral Forms
• Decreased particle size, enhanced
absorption.
• Increase bioavailability.
• Increase half life.
• Decrease drug destruction.
• Enhanced absorption if taken with food.

13. Transvaginal
• Has the value of targeted delivery by
endometrial diffusion with minimal side
effects as been mentioned.
• ??? Serum level of drug, tissue???

14. Value
• Decreased side effects ( only fatigability
and some dizziness )
• Similar action to endogenous progest. .
• No mood affection.
• Improves pregnancy outcome.
• No androgenic effect.
• No fluid retention
• Not affecting HDL level.

15. In gynecology
• Abnormal uterine bleeding; amenorrhea,
bleeding, cycle dating, .
• Contraception.
• Endometriosis, ttt , prevention.
• LPD.
• Menstrual disorders:
• Spasmodic dysmenorrhea.
• Cancer ttt and prevention
• HRT.

16. In Obstetrics
Pro = For
Gesterone = pregnancy
Anti-progestins can induce ab. & cx ripening
Prog. withdrawal prepares ut. For labour
Prog. prepares ut. for uterotonic agents
• Threatened abortion.
• Recurrent abortion.
• PTL.
• Excluding other specific factors.

17. H0W ?
• Prepares endometrium for implantation
and pregnancy continuation.
• Decreases immunity to prevent fetal cells
rejection.
• Decreases myometrial activity by
decreasing PGs, response to oxytocin and
decreases natural imm. Suppression.
• Blocks type1 collagen degradation in Cx.
• Prevents apoptosis in fetal membranes,
so may protect from PROM.

18. • Cochrane meta analysis early in 2011
suggested that, progesterone
supplementation has beneficial effects in
patients with recurrent pregnancy loss.
• A Cochrane review 2013 (225 case, 4 small
trials) reported lower abortion rate among
progesterone users in first trimester.
• Cochrane 2014, use of progesterone may
prolong pregnancy, attenuate cx length .
• The small number of patients and trials is
questionable, debate is still present.

19. • Value of progesterone intake compared
to placebo effect must not be
underestimated in an anxious patient.
• Many other studies confirmed the value of
progesterone in preserving Cx. Length
and decrease rate of spontaneous early
PTL while many other studies not !!!!.
• Progesterone is considered as a drug of
choice which is better than doing nothing.
• An ounce of prevention is better than
pound of cure.

20. Thank you