1)
.ABC OF Oestrogens : A refresher course for members working at
periphery:-Types of Oestrogens in the Indian market: A) Ethinyl
Oestradiol –mostly as COC B) Oestradiol Valerate-mostly available as oral
Tablets e.g. Trade names are E D Val 2; Evadilol, 3) Equine estrogens-safe-e.g.
Premarin 4) Natural Oestrogens-Abbott.
Fortunately .Diethyl
stilboesterol, like Quinestrol is
also not available in Indian market
2)
While prescribing oestrogen alone or in
conjunction with Progesterone –do we afford time to select the best suitable
friendly but effective oestrogen for
that woman and for that diseases for whichthe drug is prescribed ? Let’s have
of a look on types of Oestrogens available in Indian Trade: Let us be acquanatied
who is who! What oestrogen for what disease So far in descending potency, the
oestrogens used in trade can be arranged in flowing order:1) EE(Ethinyl Estradiol)-most potent
-Lynoral Tablet 0.01 mg / 0.05 mg 2) Oestradiol –used in subfertility
for improving ET as oral Tablets . Used as Valerate salt. Actually E2 is
17-beta estradiol which stands in between very active pharmacological potent EE
and CEE(less potent). 3) CEE- Premarin
Tab-commonly used for secondary amenorrhoea. 4) Oestriol (E3)-Evalon. Oestriol
oral / vaginal form is most innocuous and safe for months /Years.
Efficacy
of different estrogens in body varies from one woman to other: The reasoning of one gene to one
protein synthesis does not hold good in
cases of oestrogens as density receptor and down regulation / up regulation of
cell kinetics varies.;-The differences between the various products lie in the
specific estrogenic substances they contain.
Oral oestrogens even
in identical dose, in some cases, they affect one part of the body more than
another. For the most part, however, estrogen products are interchangeable, as
long as differences in dosage are taken into account.
Enzymes in human
Endometrium, Local production of bioactive estrogens & correlation of ET with serum oestrasiol
: “The understanding of Thickness of Endomatrium”:- Endometrium contain variety of hormone-producing enzymes and coenzymes . Activity of
endometrial enzymes varies in diff women even amongst sisters. Such enzymes are
1) Sulphatase which converts inactive
oestrone to active estrone ; 2)
aromatase and 3) 17 delta- OH steroid dehydrogenase (HSD).These last two
enzymes cause conversion of all types
of androgens coming to endometrium via local circulation e.g. Androstenedione, T4 to bioactive oestradiol.
That is one reason why PCOS women (better
termed as Androgen Excess disorders)à do exhibit thick ET almost all times.
Therefore the
thickness of Endo does not always correspond with the serum E2. Even if
stimulated cycles oral replacement of E. Valerate for thin ET on day 19-12 at
the dose of 8mg OD schedule fail to improve ET. Even in IVF settings inspite of
high dose of Gonadotrophins ET remains poor thereby compelling the specialists
for Freeze à than Transfer in subsequent cycles.
Therefore Ladies and gentlemen –ET
depends partly on the activity of such enzymes, their potency , in
addition to E2 Receptor population of estrogens (up regulation/ down
regulation)/ !!
Locally produced
Oesradiol, therefore, play a major role
in thickness of Edo.--> May be one of the cause of AUB.
Researchers have documented that Progesterone
given systemically or as LNG-IUS does case diminution of all three enzymes
quoted above thereby inactivate the quantum of local synthesis of estradiol and
estrone. Progesterone therapy therefore à cause availability of less bioactive
estrogens,
2) What are the routes of administration at our
disposal?? Preparations & Route of adminisarion of oestrogen either as
immunotherapy or with Progesterone? - 1) Oral route-mostly, 2) Vaginal route as
creams-pessary, 3) Transdermal 4) Transdermal System)5) IM –Inj Progynova.& Combined E & P as
contraceptive On monthly basis. What is the most common indication of
consumption of oestrogens? Indications of Oestrogens as a single agent or as
COC with Progesterone?? As oral contraceptives B) treatment of DUB C) Tr of PMS
D) Delaying the dates of period –social reasons E) Dysmenorrhoea –not
responding to analgesics noncontraceptive benefits of Oral contraceptives. F)
Endometriosis-Tricycling particularly.
The rare uses of COC:
- Hirsutism, Pretreatment before IVF/IUI to decrease the level exaggerated LH/
Androgens. Osteoporosis,
abnormal bleeding of the uterus, vaginal irritation, female castration, and
Turners syndrome. Estrogens may also be prescribed for birth control. They are
effective as a "morning after" contraceptive but should only be used
as an emergency treatment because of the damage they can cause to developing
fetuses.
Limitations
of Oestrogen therapy?
There is no evidence that these drugs are effective for nervous symptoms or
depression occurring during menopause: They should not be used to treat these
conditions; they should be used only to replace the estrogen that is naturally
absent after menopause.
Types of oestrogens:
Though total six types of estrogens are available -only 3 are actually present
in significant amounts: estrone, estradiol, and estriol. E-1 Estrone is the
most potent of the three and is the major estrogen produced by the ovaries. E-2
17beta Estradiol is the most prevalent and is naturally modified to estrone,
which is then turned into E-3 estriol, the least potent of the three. All of
the Estrogens listed in this section will produce equal effects and side
effects when their doses are equal, taking their various potencies into
account. More potent medicines require a smaller dose to produce the same
effect. E-2 is the most prevalent estrogen produced by the ovaries prior to
menopause.
COC related
possible Health Risks.
Myocardial Infarction:-...2) Cerebral Ischemic Stroke.
3) Cerebral hemorrhagic Stroke. 4) Deep
venous Thrombosis. 5) Pulmonary Embolism. ?6) Breast Cancer. ?7) Cervical Cancer.
development of
blood-clotting disorders, liver cancer or other liver tumors, high blood
pressure, glucose intolerance (symptoms similar to diabetes) or worsening of
the disease in diabetic patients, unusual sensitivity to the sun, and high
blood levels of calcium.
Side effects of Drug Vis- a- vis Health risks induced
by the drug consumes: Known health risks of oestrogens if used for months
together: At the outset we must be clear that side effects of a drug should not
be confused with health risks of the client (patient-who is consume sing the
drug/ device somebody is using) --either for illness or for prophylaxis. Of
concern is particularly metabolic and coagulatory side effect of oestrogens.
Whenever we are using oestrogens for 6 months and beyond these questions should
lurk in our mind. We have to take into
consideration about side effects of estrogens Vis-a -Vis desired benefits out
of the drug. Needless to mention that we always calculate the “Risk/Benefit
ratio” in such a setting.
Vaginal estrogen creams may stimulate bleeding of the uterus. They can also
cause breast tenderness. Vaginal discharge, and withdrawal bleeding (if the
product is suddenly stopped). Women with endometriosis may experience heavy
vaginsl bleeding.
Top of Form
Side effects of
COC:-The most common side effects include nausea, vomiting, breakthrough
vaginal bleeding, vaginal spotting, changes in menstrual flow, no menstrual period during and after estrogen
use enlargement or tenderness of the breasts, swelling of the ankles and legs,
loss of appetite, weight changes, retention of water, abdominal cramps, and
feeling of bloatedness. The estrogen patch can cause skin rash, irritation, and
redness at the patch site.
Less common side
effects are, , enlargement of uterine fibroids, vaginal infection with Candida,
a cystitis-like syndrome, , loss of scalp hair, and development of new hairy
areas. Lesions of the eye and contact-lens intolerance have also been
associated with estrogen therapy. Rarely one may have may experience migraine
headache, mild dizziness, depression, and increased sex drive (women) .
Rare side effects
include stroke, blood-clot formation, dribbling or sudden passage of urine,
loss of coordination, chest pains, leg pains, difficulty breathing, slurred
speech, and vision changes. Men who receive large estrogen doses as part of the
treatment for prostate cancer are at a greater risk for heart attack,
phlebitis, and blood clots in the lungs.Estriol (E3) is
metabolically / innocuous so also from the standpoint of coagulator parameters.
We always do Minimal/ No Hypercoagulable sates.E3-Estriol is of lest potent and
mostly used for local application –Cream/Ointments --either as prophylaxis/ to
prevent urogenital atrophy or to prevent senile vaginnits/ recurrent urethritis
in postmenopausal women. Occasionally this Oestriol is used along with
Probiotics-as vaginal pessary in idiopathic BV (Bacterial Vaginosis) in
resistant cases where Metranidazole, Clinidamycin have failed.
We , busy practitioners often forget the
Relative contraindications of estrogens alone/ COC . Honestly speaking, some of us do
prescribe COC/ Oestrogen unnoticing:-e.g.1) HTN 2) Smokers 3) > 10 yrs COC
use continuously. 4) Originally –Normotensive but with the use of COC/ E2-there
is gradual rise of BP 5) Dyslipidaemia. We often forget to limit the duration
of therapy in such cases .This is rush at OPD or at Clinic. As a result some
women if gain benefit out of COCà continue to
take COC for long time without further consulation which is to be discouraged.
Women, especially those over 35, who smoke cigarettes and take an Estrogen have
a much greater chance of developing stroke, hardening of the arteries, or blood
clots in the lungs. The risk increases as age and tobacco use increase
Absolute
contraindications: 1) DM with retinal/ CAD who are on Insulin 2)CRF 3) had P/H/O VTE 4) Gross/Moribund Obesity 5) Had Heart attack 6) On Tr for Ca
Cx / Breast Ca.
Newer
& safer Oestrogens in oral Pills----Widening the horizon of choice of
Contraception: Can we come out of synthetic
oestrogencontING pills?? Such Pills (COC containg Ethinyl Oestradiol) may be
avoided in contraceptive selection should we not go for Women friendly /
metabolic friendly Oestrogens whole choosing Pills for Indian women??
Your views please:-We are aware that
synthetic oestrogens (EE-ie. Ethinyl oestradiol) is globally the most commonly
used estrogen in COC preparations.
But this
type of Oestrogen salt (EE) is metabolically a bit harmful and should not be
used for long time specially in women
with some medical diseases like DM, those with exaggerated risk of VTE,
hypertension, hepatic diseases , ages> 40 yrs, dyslipidaemia, & smoker.
Put in such a situation, earlier the contraceptive seeker was deprived of the
benefit of Oral pills. Instead such medically sick women were offered to choose
TCu-380A or Tubectomy or even the least effective Barrier methods. Now the fact that more safe oestrogen i.e.
Estradiol valerate is being used in some countries as estrogen component in COC
(though it is costly) in lieu of synthetic EE -we can offer such sick women
valerate containing COC or even more new
COCs –( COC with absolutely Natural Oestrogens
)--which are metabolically more safe than valerate containg COC.
This policy
if adopted by us and financially supported by Govt. (subsidy) then popularity
of COC may be doubled than the present rate of COC use in our country... There
may not be any incidence of heart attack/ cerebral thrombosis/ venous
thrombosis in women with the use of newer oestrogen containg COC. Many women
are afraid of taking COC for the fear of such dreaded complication which they
have read in media/prints. Such safer oestrogen containg pills are more
relevant in women who are already at increased risk of Heart attack or DM
prevails.
We
can now safely prescribe to such at risk women Valerate containg COC.Now about
the widespread use of Oestrogen Valerate: The following are the: - What
are the currently licensed products used as OCP with natural Oestrogens abroad?
A) Pills where natural oestrogen used is Oestradiol Valerate are at UK= Qlaira, Klaira (this product is originally developed by Teva and later Merck (originally Organon) also had an agreement with Teva about marketing sratetegy,
At USA= Natazia (Bayer). In such formulations the progesterone used is Dienogest.
One should remember that E. Valerate is a prodrug and is very quickly converted to natural oestrogen (E2).
B) Pills containing Plain Oestradiol (E2): No salt at all= Zoely (MSD). In such formulation the progesterone used is nomegestrol which is commonly used in contraceptive implants.
A) Pills where natural oestrogen used is Oestradiol Valerate are at UK= Qlaira, Klaira (this product is originally developed by Teva and later Merck (originally Organon) also had an agreement with Teva about marketing sratetegy,
At USA= Natazia (Bayer). In such formulations the progesterone used is Dienogest.
One should remember that E. Valerate is a prodrug and is very quickly converted to natural oestrogen (E2).
B) Pills containing Plain Oestradiol (E2): No salt at all= Zoely (MSD). In such formulation the progesterone used is nomegestrol which is commonly used in contraceptive implants.
-10)
Differential Proliferation of one type of cells where many types of tissues are
existent:-
11) Anybody has tried Bazedoxifene? It is being used abroad with the approval
of FDA in combination with Conj Estrogen (CEE-Conj Equine Estrogen).
Oestrogens & VTE: -- Estrogen cause slight increase in
fibrinogen and by that promotes slightly of the contraceptive steroids we
should remember that it is the estrogen which causes Hypercoagulable state and
is primarily attributed for DVT and allied thrombosis during OCP intake. The
risk of VTE is directly related to dose of E but the OCP induced risk of VTE IN
PREGNANCY IS LOWER THAN THE RSIK ASSOCIATED WIRH EVEN LOW-DOSE COC.
Inherited Thrombophilia:-
But as we know in some countries factor Leiden mutation, Protein-C /S
synthesis disorders (DEFICIENT PRODUCTION) or prothrombin mutation disorders
are to the extent of 0.5 to 5% of general population in those countries. In
such countries it will be prudent to screen women who candidates for inherited
thrombophilias and refrain from prescribing OCP if screen +ve or family is +ve/
or she herself has already suffered from DVT in the recent past... This is not
true for our country.
Acquired APC resistance: - APC resistance: - APC naturally down
regulates the thrombin formation. APC therefore is a naturally occurring the
prevalence of DVT in acquired APC resistance is 6/10,000 women in reproductive
years. Who is not.OCP? But if one uses OVP then the prevalence goes up to
Increased APC resistance can invite thrombosis.
PCOS & Venous thrombosis:- using Thrombosis can occur at varying
sites including legs, thigh veins, lungs, eye ,intestines or heart
Natural estrogens with Dienogest are QLARIA
Natural
estrogens with Dienogest are QLARIA
E2 valerate
with Dienogest as progesterone as OCP:-Brand names are:-Klaira, Natazia. –all
quadriphasic
D).
Progesterone Receptor Modulators
The side
effects of Visanne (dienogest-Bayer) are Chloasma, depression, irregular
bleeding, ovarian cyst formation. Wt Gain, Nausea. . Will 1 mg dose (anovulatory doe) will be
able to manage endometriosis.
Will
combination of Dienogest with natural
Oestrogen be at all effective to control endometriosis, keeping in mind
that the very diagnosis has not been confirmed in this case? The idea of
prescribing Dienogest containing natural oestrogens stems from the fact such
drugs will ensure monthly bleeds. I understand many gynaecologists will
purposefully intend to avoid EE
(synthetic agent) which is very potent and will exert more harmful effect on
the existing pathology (endometriosis).
Such
combinations of natural oestrogens with
Dienogest are QLARIA –polyphasic preparations (marketed again by Bayer) and
the Obstr. Component used is E2V (valerate). The other trade names are Klaira,
Natazia. –all quadriphasic.
I appeal some
ART specialist to consider for trial on couple of cases particularly in women
where fertility is not an issue (therefore no question of loosing time to
conception – post Tubectomy endometriosis).
Bayer Co. / Endometriosis
Society of India/. FOGSI can help in funding if may be approached.
What about
other Progesterone Receptor Modulators in this young adult? Will any Indian Doctor become team leader in
study of ULIPRISTAL ACETATE (UPA) in Pel? Endometriosis.
Dienogest. Brand Names are: - Visanne (Dienogest-Bayer).
Ulipristal as ECP. EllaOne.
AS ECP:- It is an FDA
approved drug for Emergency contraceptive used as 30 mg single dose as post
coital contraceptive (Morning after pill). Research has confirmed that
ULIPRISTAL ACETATE (UPA) is more effective that LNG 1.5 mg. The trade name is
EllaOne. –
Realtive Contraindications of minipils:--Regarding the apprehension raised by
members about the use of minipills progesterones( though WHO has
referred to LNG and not specially to Dienogest) or even COC in a case impaired
hepatic function (fatty liver/ NAFL- non-alcoholic fatty liver) :---- may I
draw attention to the fact that WHO medical Eligibility criteria put use of LNG
as category 2 risk only in cases with 1) Non vascular DM 2) DM with nephropathy 3) P/H/O preg Cholestasis (cat 1 risk-no
risk)/ past COC related Cholestasis(Cat 2 risk 4)
Acute viral hepatitis ! (Not to
speak of Chr carriers) -believe me I am
quoting from original WHO BOOK, Ed. 2010, ISBN 978 92 4 15388 8) p. 53 5) Valvular heart disease ) Multiple risk factors for arterial CVS
disease (!) 7) Controlled HTN with
drugs. ) no age bar 9) Smokers of all ages (!). 10) Obese women 110 DVT on oral
anticoagulants (!) & Myomas.
Such views have
also been expressed by other academic bodies like Clinical Guidance.
Contraception for women aged over 40 yrs by UK, Australia and USA separately.
I am not very sure whether such liberal use
will be safe for dienogest too. 3) Another issue- The compulsion of use of a
drug for treating disuse as using dienogest cannot be equated to contraceptive
prophylaxis where other options are available.
Again ICMR and
its control Six population research centers, “Human Reproductive Research
centers” = Total such centers are 31 in India,
20 ICMR study centers can forward to ace o pilot study on this issue.
ENDOETRIOSIS is a nightmare to ART specialists!!!
There are several Types of oestrogen used in Pharma
industry:- A) EE(Ethinyl Estradiol)
–most potent I call it handle with care so far as VTE is considered in
unfavourable alterations in coagulatory proteins synthesized from liver B) CEE-e.g. Manufactured from Pregnant Mare Urine: Trade name Premarin- available in strengths 1.25 mg,
0.625 mg, & 0.03 mg. Tablets of the lowest
strength (0.03 mg ) ,however are
most commonly used along with MPA(Medroxy progesterone-2.5 mg / even 5 mg / Duphaston either as sequential or
continuous combined as it is commonly
called HRT for months/ years with
minimal monitoring / harm to the women concerned .In fact CEE is less potent
than EE(EE=Ethinyl Oesradiol) which, as I said, is commonly used in COC/COCP. I repeat by saying
EE is very potent. C) Oestradiol:-17 β oestradiol is Natural Estrogen secreted
from Ovaries, Adrenal and Adipose tissues. The issue of HRT & choice of oes COC related Health Risks.
Myocardial Infarction:-Cerebral Ischaemic
Stroke.
Cerebral hemorrhagic Stroke.Deep venous
Thrombosis.Pulmonary Embolism.Breast Cancer.Cervical Cancer.
Oestrogen: Dose
& duration: - Sex
hormones are implicated in the immune response, with estrogens as enhancers at
least of the humoral immunity and androgens and progesterone (and
glucocorticoids) as natural immune-suppressors. Several physiological,
pathological, and therapeutic conditions may change the serum estrogen milieu
and/or peripheral conversion rate, including the menstrual cycle, pregnancy,
postpartum period, menopause, being elderly, chronic stress, altered circadian
rhythms, inflammatory cytokines, and use of corticosteroids, oral
contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen
ratios and related effects. In particular, cortisol and melatonin circadian
rhythms are altered, at least in rheumatoid arthritis (RA), and partially
involve sex hormone circadian synthesis and levels as well. Abnormal regulation
of aromatase activity (i.e., increased activity) by inflammatory cytokine
production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the
abnormalities of peripheral estrogen synthesis in RA (i.e., increased
availability of 17-beta estradiol and possible metabolites in synovial fluids)
and in systemic lupus erythematosus, as well as the altered serum sex-hormone
levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids
of RA patients, the increased estrogen concentration is observed in both sexes
and is more specifically characterized by the hydroxylated forms, in particular
16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous
hormone. Local effects of sex hormones in autoimmune rheumatic diseases seem to
consist mainly in modulation of cell proliferation and cytokine production
(i.e., TNF-alpha, Il-1, and IL-12). In this respect, it is interesting that
male patients with RA seem to profit more from anti-TNFalpha strategies than do
female patients.
Spontaneous
miscarriage and preterm delivery are common complications of pregnancy.
Pro-inflammatory cytokines have been shown to be associated with recurrent
spontaneous miscarriage (RSM) and preterm delivery (PTD) and these have led to
exploration of ways to down regulate pro-inflammatory cytokines and/or to
upregulate anti-inflammatory cytokines. Progesterone-induced blocking factor
(PIBF) is a molecule with inhibitory effects on cell-mediated immune reactions.
We have ascertained the effects of PIBF on secretion of selected type 1 and
type 2 cytokines by peripheral blood mononuclear cells from healthy
non-pregnant women, women undergoing normal pregnancy, women with unexplained
RSM and women with PTD. Peripheral blood mononuclear cells from 30 women with a
history of unexplained RSM, 18 women undergoing PTD, 11 women with normal
pregnancy and 13 non-pregnant healthy women were stimulated with a mitogen in
the absence and presence of PIBF after which the levels of cytokines released
into culture supernatants were determined by ELISA. Production of the type 2
cytokines IL-4, IL-6 and IL-10 by lymphocytes from the RSM and PTD groups and
of IL-4 and IL-10 by lymphocytes from healthy pregnant women was significantly
increased upon exposure to PIBF, while the levels of type 1 cytokines were not
affected. Ratios of type 1:type 2 cytokines were decreased, suggesting a shift
towards Th2 bias. PIBF did not affect cytokine production by lymphocytes from
non-pregnant women. Thus, PIBF acts on lymphocytes in pregnancy to induce a
type 1 to type 2 cytokine shift by upregulating the production of type 2
cytokines.
PMID:
19371956
[PubMed -
indexed for MEDLINE] Good/Ill effects of oestrogen varies: The
metabolism of oestrogens in body varies from one women to other, from one group
of population to other (Ref: Goldzieher, JW, Am J Obstet & Gynaecol
163:318,1990). There is even a range of variability at different sampling times
within the same individual. Therefore it is not surprising that the same dose
can cause side effects in one individual (Vaginal adenosis, Neoplasia,
testicular cancer as stated by members) and not in others.(source: ‘A Clinical
Guide for Contraception’, 4th
Ed, by Leon Speroff, Philip D Darney. Lippincott, pp; 31)
Now about the
widespread use of Oestrogen Valerate: = May I mention the followings: - What
are the currently licensed products used as OCP with natural Oestrogens abroad?
Pills where natural oestrogen used is Oestradiol Valerate= B are at UK=
Klaira, Klaira (this product is originally developed by Teva and later Merck
(originally Organon) also had an agreement with Teva about marketing sratetegy,
At USA= Natazia (Bayer). In such formulations the
progesterone used is Dienogest.
One should remember that E. Valerate is a prod rug and
is very quickly converted to natural oestrogen (E2).
Pills containing
Oestradiol (E2) = Zoely (MSD). In such formulation the progesterone
used is nomegestrol which is commonly used in contraceptive implants. By the
way if one tries to avoid Parenteral Oestrogens what are other types of natural
oestrogen? Which can be considered in lieu of Inj. Oestradiol Val. Thanks?
Good/Ill effects of
estrogen vary: The metabolism of oestrogens in body varies from one woman to
other, from one group of population to other (Ref: Goldzieher, JW, Am J Obstet
& Gynaecol 163:318, 1990). There is even a range of variability at different
sampling times within the same individual. Therefore it is not surprising that
the same dose can cause side effects in one individual (Vaginal adenosis,
Neoplasia, testicular cancer as stated by members) and not in others. (Source:
‘A Clinical Guide for Contraception’, 4th Ed, by Leon Speroff, Philip D Darney.
Lippincott, pp; 31)
Can synthetic oestrogens be avoided in COC products?? We are aware that synthetic oestrogens are bit harmful and should not be used for long time in women with some medical diseases like DM, those with exaggerated risk of VTE, hypertension, Dyslipidaemia. In such a situation, earlier the contraceptive seeker was debited of the benefit of Oral pills. Instead they were asked to choose TCu-380A or Tubectomy. Estradiol valerate is used in lieu of synthetic EE in COC.Now about the widespread use of Oestrogen Valerate: The following are the: - What are the currently licensed products used as OCP with natural Oestrogens abroad?
A) Pills where natural oestrogen used is Oestradiol Valerate are at UK= Qlaira, Klaira (this product is originally developed by Teva and later Merck (originally Organon) also had an agreement with Teva about marketing sratetegy,
At USA= Natazia (Bayer). In such formulations the progesterone used is Dienogest.
One should remember that E. Valerate is a prodrug and is very quickly converted to natural oestrogen (E2).
B) Pills containing Oestradiol (E2) = Zoely (MSD). In such formulation the progesterone used is nomegestrol which is commonly used in contraceptive implants. By the way if one tries to avoid Parenteral Oestrogens what are other types of natural oestogen?
May I draw attention to all concerned that
Can synthetic oestrogens be avoided in COC products?? We are aware that synthetic oestrogens are bit harmful and should not be used for long time in women with some medical diseases like DM, those with exaggerated risk of VTE, hypertension, Dyslipidaemia. In such a situation, earlier the contraceptive seeker was debited of the benefit of Oral pills. Instead they were asked to choose TCu-380A or Tubectomy. Estradiol valerate is used in lieu of synthetic EE in COC.Now about the widespread use of Oestrogen Valerate: The following are the: - What are the currently licensed products used as OCP with natural Oestrogens abroad?
A) Pills where natural oestrogen used is Oestradiol Valerate are at UK= Qlaira, Klaira (this product is originally developed by Teva and later Merck (originally Organon) also had an agreement with Teva about marketing sratetegy,
At USA= Natazia (Bayer). In such formulations the progesterone used is Dienogest.
One should remember that E. Valerate is a prodrug and is very quickly converted to natural oestrogen (E2).
B) Pills containing Oestradiol (E2) = Zoely (MSD). In such formulation the progesterone used is nomegestrol which is commonly used in contraceptive implants. By the way if one tries to avoid Parenteral Oestrogens what are other types of natural oestogen?
May I draw attention to all concerned that
Natural estrogens with Dienogest are QLARIA
1.
Natural estrogens with Dienogest are QLARIA
E2 valerate
with Dienogest as progesterone as OCP:-Brand names are:-Klaira, Natazia. –all
quadriphasic
D).
Progesterone Receptor Modulators
The side
effects of Visanne
(dienogest-Bayer) are Chloasma, depression, irregular bleeding, ovarian
cyst formation. Wt Gain, Nausea. . Will
1 mg dose (anovulatory doe) will be able to manage
endometriosis.
Will
combination of Dienogest with natural Oestrogen
be at all effective to control endometriosis, keeping in mind that the very
diagnosis has not been confirmed in this case? The idea of prescribing Dienogest containing natural oestrogens stems from
the fact such drugs will ensure monthly bleeds. I understand many
gynaecologists will purposefully intend to avoid EE (synthetic agent) which is very potent and will
exert more harmful effect on the existing pathology (endometriosis).
Such
combinations of natural
oestrogens with Dienogest are QLARIA –polyphasic preparations
(marketed again by Bayer) and the Oestr. component used is E2V (valerate). The other trade names are Klaira,
Natazia. –all quadriphasic.
I appeal some
ART specialist to consider for trial on couple of cases particularly in women
where fertility is not an issue (therefore no question of loosing time to
conception – post Tubectomy
endometriosis). Bayer Co. /
Endometriosis Society of India/. FOGSI can help in funding if may be
approached.
What about
other Progesterone Receptor Modulators in this young adult? Will any Indian Doctor become team leader in
study of ULIPRISTAL ACETATE (UPA) in Pel? Endometriosis.
1.
Dienogest. Brand Names are: -
Visanne (Dienogest-Bayer).
Ulipristal as ECP. EllaOne.
AS
ECP:- It is an FDA approved drug for Emergency
contraceptive used as 30 mg single dose as post coital contraceptive (Morning
after pill). Research has confirmed that ULIPRISTAL
ACETATE (UPA) is more effective that LNG 1.5 mg. The trade name is EllaOne. –
Realtive Contraindicatins of
mnipils:--Regarding the apprehension raised by members about the
use of minipills progesterones( though WHO has
referred to LNG and not specially to Dienogest) or even COC in a case impaired
hepatic function (fatty liver/ NAFL- non-alcoholic fatty liver) :---- may I
draw attention to the fact that WHO medical Eligibility criteria put use of LNG
as category 2 risk only in cases with 1) Non vascular DM 2) DM with nephropathy 3) P/H/O preg Cholestasis (cat 1 risk-no
risk)/ past COC related Cholestasis(Cat 2 risk 4)
Acute viral hepatitis ! (Not to
speak of Chr carriers) -believe me I am
quoting from original WHO BOOK, Ed. 2010, ISBN 978 92 4 15388 8) p. 53 5) Valvular heart disease ) Multiple risk factors for arterial CVS
disease (!) 7) Controlled HTN with
drugs. ) no age bar 9) Smokers of all ages (!). 10) Obese women 110 DVT on oral
anticoagulants (!) & Myomas.
Such views have
also been expressed by other academic bodies like Clinical Guidance.
Contraception for women aged over 40 yrs by UK, Australia and USA separately.
I am not very sure whether such liberal use
will be safe for dienogest too. 3) Another issue- The compulsion of use of a
drug for treating disuse as using dienogest cannot be equated to contraceptive
prophylaxis where other options are available.
Again ICMR and
its control Six population research centers, “Human Reproductive Research
centers” = Total such centers are 31 in India,
20 ICMR study centers can forward to ace o pilot study on this issue.
ENDOETRIOSIS is a nightmare to ART specialists!!!
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