NATURAL
PROGESTERONE VS
SYNTHETIC
PROGESTERONE
Dr M. Mahalakshmi
Assistant professor
ISO & KGH, Triplicane, Chennai.
PROGESTOGENS
IN PREGNANCY
Progestogens
Progesteron Progestins
e (P4)
Endogenous Exogenous/ Synthetic
Bioidentical
Progesterone Dydrogesterone Hydroxyprogest
(oral, vaginal, (Oral) erone caproate
IM & SC) (IM)
INTRODUCTION
Role of progesterone in reproductive medicine is evolving with its suggested
clinical role for the hormonal and non-hormonal actions in reproductive
medicine.
Progesterone is an essential hormone which plays an important role in women
normal reproductive cycle
Secreted by ovaries ,placenta and adrenal glands
Essential during luteal phase to sustain pregnancy
Promotes shedding of endometrium due to its anti-proliferative endometrial
action and thereby helps in maintaining regular menstrual cycle.
Exogenous progesterone supplementation is given for treatment of secondary
amenorrhea,AUB,endometriosis, luteal phase defect, to prevent preterm
delivery
to prevent endometrial hyperplasia
ORAL NMP -SR
Oral NMP SR contains progesterone
in a methyl cellulose base.
T ½ - 18 hours
High protein binding of 90%-99%
leading to once a dosage convenience
NATURAL PROGESTERONE
Natural progesterone obtained from soy beans and Mexican
yam roots
Same chemical structure as that of physiological
progesterone found in human body
. It is considered a safer alternative to synthetic progestins
USE OF ORAL NMP IN
OBSTETRICS
Natural progesterone supplementation can help to extend the
luteal phase, increase the thickness of the uterine lining, and
improve implantation and pregnancy outcomes. And thus can
be admisntered in the following situations .
LUTEAL PHASE INSUFFICIENCY
SPONTANEOUS MISCARRIAGE
THREATENED MISCARRIAGE
RECURRENT MISCARRIAGE
PRETERM BIRTH PROPHYLAXIS – Limits the production of stimulatory prostaglandins –onset
of labour both at term and preterm is associated with functional withdrawal of
progesterone activity at the level of uterus.
Reduces symptoms of morning sickness: Progesterone can help to reduce symptoms of
morning sickness, such as nausea and vomiting, by reducing the sensitivity of the stomach
to certain smells and tastes.
THREATENED MISCARRIAGE AND
RECURRENT MISCARRIAGE
The use of natural progesterone during pregnancy is a topic of
ongoing research and debate among healthcare professionals.
Progesterone is a hormone that is essential for the maintenance of
pregnancy
In some cases, women may experience low progesterone levels
during pregnancy, which can increase the risk of miscarriage or
preterm labor.
In these situations, healthcare providers may recommend the use
of natural progesterone supplements to help support the
pregnancy.
However, the existing evidence base is largely composed of old
studies of poor quality, such as the two meta-analyses from
Goldstein et al. and Daya demonstrating a slight increase in the
rate of pregnancies that continues beyond 20 weeks with
progesterone treatment compared with placebo or no treatment .
PROGESTINS
Progestins are synthetic hormones that are structurally similar to the naturally occurring
hormone progesterone.
ACTION OF
PROGESTINS
Helps in implantation
Maintain uterine quiescence by stabilizing
lysosomal membranes and inhibiting
prostaglandin synthesis.
Inhibits myometrial contractions
Induces secretory changes in endometrium
Increases the vascularity and stabilization of
endometrium
NON HORMONAL ACTION – IMMUNO MODULATORY
or ANTI INFLAMMATORY – progesterone along with
HCG and CORTISOL inhibits the tissue rejection
and protect the conceptus.
SIDE EFFECTS OF
SYNTHETIC PROGESTIN
EXCEPT
DYDROGESTERONE
These side effects are due to their
action on androgen receptors:
Fluid retention
Decrease the HDL cholesterol level
Headache
Mood disturbances
DYDROGESTERONE
Dydrogesterone, a progestogen that has high specific affinity for
progesterone receptors, no affinity for androgen, mineralocorticoid,
glucocorticoid, and estrogenic receptors.
MECHANISM OF ACTION
1. It acts on the endometrium by converting it from estrogen primed
proliferative phase to the secretory phase thereby preparing the uterus to
recived the fertilised [Link] has a progestogenic and antiestogenic
activity.
2. Immunomodulatory action
ADVERSE EFFECTS
INTERACTIONS: anticoagulants, anticonvulsants (e.g. Phenobarbital,
phenytoin, carbamazepine), anti-infectives
Acute adverse effects
Nausea,Vomiting
Withdrawal Bleeding
Chronic or high dose can result in jaundice, headache, menstrual
irregularitis
CONTRAINDICATIONS
Known hhypersensitivity to active ingredients or excepients
Progestogen dependent malignancies (meningioma)
Undiagnosed vaginal bleeding
Special warnings:
History of abnormal bleeding, liver dysfunction / acute liver disease, break
through bleeding or spotting during therapy, porphyria
DOSAGE
Threatened miscarriage or spontaneous miscarriage - 40 mg loading lose
followed by 20 -30 mg daily continued till seven days after bleeding stops.
RPL or Habitual miscarriage - 20 mg daily from confirmation of preganancy
to twenty weeks of gestation
Safety signals of 17-OHP-C use in pregnancy and
efficacy in the prevention of preterm birth
Charles University, First Medical School, Obstetrics & Gynecology, Apolinarska 18, Prague, 128 52
Czech Republic
The use of 17-alpha hydroxyprogesterone caproate (17-OHP-C) for the prevention
of preterm birth has become rather commonplace worldwide.
It is worth noting that the synthetic progestin 17-OHP-C and natural progesterone
are not similar molecules and have different activities in a number of respects
including their effects on the myometrium [ and in their safety profile .
Natural progesterone has documented properties of inhibit- ing uterine
contractions whereas 17-OHP-C seems to have no effect on uterine
contractions .
In addition, natural progesterone has an established safety profile in the first
trimester of pregnancy from more than 11 years of continued and ongoing use in
infertility as daily progesterone supplementation and replacement in IVF cycles
THE ROLE OF PROGESTERONE IN MATERNAL AND FETAL
MEDICINE
Gian Carlo Di Renzo, Irene Giardina, Graziano Clerici, Alberto Mattei, Alia H. Alajmi & Sandro Gerli
EFFECT OF PROGESTOGEN SUPPLEMENTATION EARLY
IN PREGNANCY WITH POSTDATE LABOUR AND FAILURE
OF LABOR INDUCTION AMONG THEM
Dr. Zahraa Abdul Jaleel Murtadha,Dr. Shyamaa Abd Hassan, Dr. Reem Ali
Haddad
[Link] supplementation early in pregnancy is associated with a
higher incidence of postdate labour ( pregnancy prolongation beyond 40
weeks gestation), and progesterone is estimated to be risk factor for causing
that effect ( RR: 2.611, df: 1, P value: 0.117)
[Link] supplementation early in pregnancy is associated with higher
incidence of failed induction of labour in postdate pregnants that have been
supplemented compared to those who were postdate yet not supplemented
Role of Micronized Progesterone Versus Dydrogestron in Patients
with Threatened Abortion
Rukhsana Shaikh1 , Ayesha Jalbani2 , Shaista Lashari3 , Saeed-un-Nisa Sangi4 , Sumera
Brohi5 , Quratulain Shaikh6
In the management of threatening miscarriage or bleeding, both
Micronised Progesterone and Dydrogesterone therapies were found to be
equally effective.
Although the rate of side effects like drowsiness and giddiness was
significantly higher in women treated with Micronised Progesterone as
compared to women treated with Dydrogesterone.
So Dydrogesterone can be used as a better alternate to Micronised
Progesterone with fewer side effects
AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS
ALGORITHM FOR THE MANAGEMENT OF INCIDENTALLY DETECTED
SHORT CERVICAL LENGTH
G. C. Di Renzo et al.
A blueprint for the prevention of preterm birth: vaginal
progesterone in women with a short cervix*
Roberto Romero 1,a, **, Lami Yeo 1,2 , Jezid Miranda 1 , Sonia S. Hassan
1,2 , Agustin Conde-Agudelo 1 and Tinnakorn Chaiworapongsa 1,2
Preterm birth is the leading cause of perinatal morbidity and mortality
worldwide.
Randomized clinical trials and individual patient meta-analyses have
shown that vaginal progesterone reduces the rate of preterm delivery
at < 33 weeks of gestation by 44%, along with the rate of admission to
the neonatal intensive care unit, respiratory distress syndrome,
requirement for mechanical ventilation, and composite neonatal
morbidity/mortality score.
There is no evidence that 17-a-hydroxyprogesterone caproate can
reduce the rate of preterm delivery in women with a short cervix, and
there- fore, the compound of choice is natural progesterone (not the
synthetic progestin).
Jane Elizabeth Norman 1, Neil Marlow 2, Claudia-Martina Messow 3, Andrew Shennan 4, Phillip R Bennett
5, Steven Thornton 6, Stephen C Robson 7, Alex McConnachie 3, Stavros Petrou 8, Neil J Sebire 2,
Tina Lavender 9, Sonia Whyte 10, John Norrie 11; OPPTIMUM study group
Double-blind, randomised, placebo-controlled trial
3 primary outcomes:
fetal death or birth before 34 weeks and 0 days gestation (obstetric),
A composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and
A standardised cognitive score at 2 years of age (childhood), imputing values for deaths
Results:
After correction for multiple outcomes, progesterone had no significant effect on the primary
obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0·86, 95% CI 0·61–
1·22) or neonatal outcome (OR 0·72, 0·44–1·17), nor on the childhood outcome (cognitive
score, progesterone group vs placebo group, 97·3 [SD 17·9] vs 97·7 [17·5]; difference in
means –0·48, 95% CI –2·77 to 1·81)
Maternal or child serious adverse events were reported in 70 (11%) of 610
patients in the placebo group and 59 (10%) of 616 patients in the progesterone
group (p=0·27)
PAVEL CALDA Charles University, First Medical
School, Obstetrics & Gynecology, Apolinarska 18,
Prague, 128 52 Czech Republic
22 RCTs provided data on 11,188 neonates
The pooled relative risks of neonatal mortality were 0.69 (0.31–1.54) for vaginal
progestogen in singleton pregnancies 0.6 (0.33–1.09) for intramuscular
progestogen in singleton pregnancies, 0.96 (0.51–1.8) for vaginal
progestogen in multiple pregnancies, and 0.96 (0.49–1.9) for intramuscular
progestogen in multiple pregnancies
Pooled RR of neonatal death in the progestogen treatment group was not
significantly different from that of the placebo groups
These results are clinically meaningful as physicians are provided
with concrete evidence that progestogen treatment is a relatively
safe option for the prevention of preterm births
Helen Christine McNamara 1, Rachael Wood 2, James Chalmers 2, Neil Marlow 3, John Norrie 4,
Graeme MacLennan 4, Gladys McPherson 4, Charles Boachie 5, Jane Elizabeth Norman 6
Evaluated health and developmental outcomes of all surviving children born to
mothers who participated in a double-blind, placebo-controlled trial of progesterone
given for the prevention of preterm birth in twin pregnancies (STOPPIT,
ISRCTN35782581)
There were no differences between progesterone-exposed and placebo-
exposed twins with respect to incidence of death, congenital anomalies
and hospitalisation, nor on routine national child health assessments
89% of children were rated as having ‘excellent’ health and a further 8%
as having ‘very good’ health.
A COMPARATIVE, RANDOMIZED CONTROL TRIAL IN
PATIENTS OF PER VAGINAL BLEEDING COMPARING
EFFICACY OF ORAL DYDROGESTERONE VERSUS VAGINAL
PROGESTERONE IN SUCCESSFUL PREGNANCY OUTCOME
FOR PATIENTS WITH RECURRENT PREGNANCY LOSS
Ashish Ramchandra Kale 1, Ashwini Ashish Kale 1, Kanan Yelikar 2
A total of 200 patients were randomized to vaginal progesterone 600 mg/day (n = 100)
or oral dydrogesterone 30 mg/day (n = 100).
While 74 patients had two miscarriages in the progesterone group, 68 patients had two
miscarriages in the dydrogesterone group.
The time required for complete cessation of bleeding was significantly lesser among
patients who received oral dydrogesterone compared to those who received
intravaginal progesterone (53.90 ± 9.09 vs. 94.60 ± 7.29 h, p < 0.0001).
Numerically higher number of patients receiving oral dydrogesterone had a successful
continuation of pregnancy up to 24 weeks of gestation, as well as till full term compared
to progesterone group (70 vs. 75).
SUPPLEMENTATION WITH PROGESTOGENS IN THE FIRST TRIMESTER OF
PREGNANCY TO PREVENT MISCARRIAGE IN WOMEN WITH UNEXPLAINED
RECURRENT MISCARRIAGE: A SYSTEMATIC REVIEW AND META-ANALYSIS
OF RANDOMIZED, CONTROLLED TRIALS
(February 2017)
Gabriele Saccone M.D., Corina Schoen M.D., Jason M. Franasiak M.D.,
Richard T. Scott Jr. M.D., H.C.L.D., Vincenzo Berghella M.D.
Design:
Systematic review and meta-analysis.
This meta-analysis from the 10 RCTs, including 1,586 women, showed that progestogens in
women with at least two or three prior miscarriages were associated with lower risk of
recurrent miscarriages and seemed to be safe to use during the first trimester. Synthetic
progestogens therapy but not natural Progesterones supplementation was associated with a
lower risk of recurrent miscarriage.