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Biochemical studies with once-a-month contraceptive pill containing quinestrol-quingestanol acetate
BIOCtERICALSTUDIESWITH ONCE-A-tlONTH CONTRACEPTIVE PILL CONTAINING QUINESTROLQUINGESTANOL ACETATE
U.N.Donde, Katayun
In8titutr (Indien
&SC.,
D.aGdirkac,
for
Ph.D. R.D.,
Rerearch
F.C.P.S.
in R8produotion
Council ot flodicalRsoraroh ) 38hangir Aerwnji Stre8t, Parrl, Bombay-400 012.
INDIA
ABSTRACT
Sioahonical rtudy of a long-acting oral 8t8rOid forrulation, containing 2.0 mg quin88trol and 2.5 g qUing88tanOl 8C8t8t8, WI) unckrtak8n during 8 p8riod Of 24 month8. H8moglobin, packed cell volum8, liv8r tunotion 8tUdia8 and 88rUI prOt8in8 kV8 not 8hoUA 8iQl3ifiCallt ohanQa8 while 8iQni?iC8nt inCrma888 in 88~1 triQlyo8rid88, fr88 tetty acid8, pho8pholipidr and chol88terol w8r8 ob8erved during the therapy. Th8 8lrvation in 8arum lipid8 Oaa allort ot the rimilar Mgnitudr aa ob88rv8d in daily combination pillr.
Accepted
JUNE
for
1975
publication
VOL. 11 NO. 6
April
2,
1975
681
CONTRACEPTION
Several publications have reported on the acceptability and clinical ePf icacy of quinastrolquingastancl (QQ) as a once-e-month contraceptive pill (l-4,6). However, the biochemical studies with QP are ssldor reported (5,6). Puinestrcl, i.e. sthinyl eatrsdiol 3-cyclopentyl ether, is an estrogen which has prolonged activity in animals (7) and in man (8). APtar absorption, it is stored unchsngsd in the body Pat and is released subsequently and mstsbolirsd to conjugates OP ethinyl estrsdiol. Puingeetsnol scatsts ie the 3-cyclcpentylenol ether derivative OP ncrethindrone acatate. A combination oP quinestrol and quingestanol acetate taken once-a-month has been Pound to have pregnancy rstss ot 1.9 to 0.2 per 100 women ysars (l-4,6). DurinQ our clinical trial8 ot ths once-a-•onth pill, it uas thought morthuhile to study the metabolic ePPscts and to compare them with those obtained during the therapy with the daily combination pill. The paramstsrs employed in the study were hemoglobin, packed cell volume, serum total protein, albumin, globulin, GOT, GPT, alkaline phosphatase, thymol turbidity, triglycsridea, phospholipids, tree Patty said8 and cholesterol. Thsss investigaticne mere carried out prior to ths therapy and during the therapy at epeciPic tine intervals in a group of’ Yo~n mho took the once-a-month pill (quinestrol 2.0 mu and qUinQs8tanOl acetate 2.5 ag ) tor contraception. RATERIALAN0 PKTHOOS blomen sttending Pamily plsnninp clinics attached to the Institute tar Research in Reproduction, Sombsy, were selected Por the studies. Theeo women belonpad to the lower socio-economic groups. The msan age, psrity and body wight in these women wera 26.8 + 4.8 years (range 18 to 44 years ), 3.33 + 1.7 (range 0 to-8 ) and 46.8 t4.05 kq (range 32.5 to 56.5 reopeztively.
kg),
The Pirst once-a-month pill YSS given on the 2nd day oP the menstrual cycle. The second pill ma8 given on the 22nd day of the same cycle. Thsrsstter, the pills uera given every 28th day Prom the last pill. Tha pills ware taken by the uomen in ths clinics. HsmoQlobin, packed cell volume and liver tunction studies were ot serum proteins csrriad out trom August 1971, while estimations and lipids wers started in November 1971. The csses invsstigatsd up to December 1973 are included in the study.
682
JUNE 1975
VOL. 11 NO. 6
CONTRACEPTION
The biocheaical paremeters were estimated in drawn in the morning before breakfast following 8 fasting period of at leest 12 houre. The blood sanpler heelscollscted botoro starting the therapy and r8r8 repeated after the ingoation of 6,12,18 and 24 pills. Sanplee uere analyaed for hemoglobin (9), packed cell volum8(9), asrutsGOT (lo), GPT (lo), triglycoridee (lo), phoapholipida(lO), thymol turbidity (ll), chol8eterol (ll), alkaline phosphateee(l2) and tree tatty eoids (15,14). In 66 women the pre-therapy blood eSlSp188Uere aveilable for 8nalySi8. In addition to pre-therepy valuee, the blood eamploe obtained 8t the initial Visits of the women attending family plenning clinics were 8nSly88d to obtain control balU88 for each Of the biochemicel p8rSmOtSrS. G8r8 was taken to 888 that these womn had not taken eny ateroidel contraceptive8 previously but had used conventional contraceptivee, such se condom, diaphragm, jslly, eto. A total of 240 such eampleo from women between the age group 19 years to 55 years wsre analyaad. Beaides control va1ue8, the pre-therapy value of 88Ch Caa8 8180 88rVed 88 hsr Own Control when eV8ilabl8. blood
samples
The 8tetistical evaluetion of the data for each group calculetion of the wan etanderd deviation and standard error of th8 mean. The signi?icanoe of the difference of mane use calculated by Fishorb t t88t idhileth8 SighifiOanCe O? th8 InsanOf the diffSrehC88 wee calculeted by Students' t t88t Using tuo-tail probability tablee. includsd
RESULTS
The results of the biochenical inveetigations are ahown in T8bl88 I and II. It can be seen that hemoglobin 8nd packed call volume u8r8 not eigni?icantly 8ltSred during the therapy. Similerly, there uaa no oigniticent variation in liver function tretr. Ssrun total protein8 and albumin level8 uers alightly, but not signiticently, ihor888ed during the ingestion of the pills. The results of serum lipids in 17 women who were continuously followedup for 2 years h8V8 been ahoun in Table II. There wee 8 SignifiCaht elevation in all the lipid fractions during the therspy. Serum triglycerides and phoepholipids, aftsr the ingsetion of 12 pills, uera loss than those after the intake of 6 pilla.
JUNE
1975
VOL. 11 NO. 6
683
Albumin
Globulin(gm$)
Serum
Serum
Serum A:G Ratio
Total Proteinajgmj)
Serum
(918% )
Thymcl Turbidity (Units)
Serum
1.49 ,+ 0.04
2.75 + 0.12
4.10 + 0.12
6.05 + 0.11
2.0
2.90 2 0.04
(Unite) Alkalina Phoaphataaa
Serum
1
1.20t0.03
3.16f0.13
3.72~ 0.11
6.06+ 0.10
2.3
3.15+ 0.03
0.0 + 1.15
,+ 1.10
9.0
CPT(Unite )
21.0 + 1.01
30.5 2 1.23
12.0 2 0.55
Pra-therapy (66)
2 1.63
2 1.21
Serum
19.2
37.6
12.04 ,+ 0.40
COT(Units )
1
Normal Controls (240)
Serum
Packed call volume($)
Blood HenoQlobfn (Qme d )
Eatimetion (Nuaber of Caaee )
RESULTS Of 0IOCHE~ICAL INVESTIGATIONS (lean ,+ S.E. )
TABLE I
I
1.40+0.04
2.07t0.11
4.0420.13
6.91_+0.00
2.4
3.302 0.04
9.3 + 1.25
22.1 + 1.65
40.3 2 1.03
I
1.21t0.04
3.25~0.09
3.0020.11
7.13+0.11
2.3
3.15+0.04
9.7 + 1.32
22.3 2 1.03
37.5 2 1.41
6 to 12 pills 12 to 24 pills (65) (17) I I 13.5 + 0.61 12.0 * 0.50
CONTRACEPTION
TABLE II SERIJN LIPIDS IN 17 WflfN WHO WERE CONTINUOUSLY FOLLOWED-UP FOR 2 YEARS (Flean f S.E. ).
Estimation
’
Pre-therapy
6 to
12 monthe l **
Serum Triglycerfdea(ag$)
95.63
2 2.16
75.9
2 1.00
29706
+11.12
408.6
212.11
1.35
241.5
+1.58
201.2
~6.35
13 to 24 months *eo 87.2
t
o**
l ,*o
Serum Free (A
fq/I
Fatty
Acids
1.95
407.6
+15.30
227.6
+. 2.95
) l **
Serum Phoepholipids (mg Z )
203.36+
l **
**I)
l o*
Serum Cholesterol
201 o4 +5.15
(mg Z )
we*
P
OISCUSSION The @canning of the literature revealed very feu reports (5,6) on the biochemical studio6 with GO a8 a once-emonth contraceptive pill. In our caaoa hemo#obin and packed cell volume have show no significant change8 during the therapy. This confirms the report of Sachs and Wolfmen (5) who, in a ante11 series, have shown insigniFicant rilroo in hematocrit values. The liver funotion which has been aerossed by estimating asrum GOT, GPT, alkalino phoephetaao and thymol turbidity have alro not ehoun significant changes. Thilr obeervatfon agrees with the report of Sechr, end IJolfmen(5). However, it conflicts with the report publiehed by Shah et al. (6) uho observed significant elevations in aorum CPT and’--alkaline phosphatase in uoemn taking the once-a-month pill.
JUNE 1975
VOL. 11 NO. 6
685
CONTRACEPTION
In our oasas, aarum~liplda uara 8fQniPicantly alavatad during the therapy. The rise uaa a~ora aPter the ingaation of 6 to 12 pills than aPtar 15 to 24 pills. The incraaaa in p~aama lipids and lipoproteins has bean reported by Sachs and Woltnan (5). Pravioua atudias carried out by ue (15) and others (96,17) have ahoun that, in uoaan taking daily oral combination contraceptives, the lavale oP asrum triglycaridaa, Praa f8tty acids, phoapholipida and cholesterol uara significantly elavatad. The increase in serum triglyoaridea has bean shot& to be due to fRpSir8d post-haparin lfpolytic activity. This iRpairmant is due to aoquirad haparin resistance (15). This aPPacta has been uinly attributed to the aatrogan coaponent of the pill (lg,20). The aetrogan corponant OP PO is 2.0 mg athynyl eatradiol 3ayalopantyl other which ia biologically more active then athynylaatradiol aa Giannlna and Reli (7) found that at all the doeaa tha J-ayolopantyl athar derivativa of athynyl eatradiol was mora aPtactive than athynyl aatradiol in atinulating utarina grouth. It appaara troa tha raaukta that PO combination produced aiailar ohengaa in serum lipids as reported in the caaaa taking daily combination piLla. In none of tha Eases did serum lipids axcaad tha uppar limit of normal. We found that the dropout rata in our clinics attar 12 pills uaa very high as seen by the small nua.bar oP caaaa on whom the taata uera carried out. The nonmaa 0P greater significance acceptability of this pill, tharetora, than the metabolic atfacts in the clinical trials.
ACKlmWLEOGfnK#T Tha authors aro gratatul to clinic dootora, aapacially Dr. S.S. Gikahit and Or. S.J.Kora, tar ratarring Chair ~4888. Appreciation is alas axpreaaad t0 tha social uorkara without uhoae aubatantfal motivation thia study umuld not have baan poaaibla.
686
JUNE 1975
VOL. 11 NO. 6
CONTRACEPTION
REFERENCES 1.
Barman, E. Tha once-a-month pill. J. Raprod. fled. 5 x 57-42 (1970).
2.
A., Oaorio, Guiloff, E., Berman, E., Rontiglio, and Llyod, L.ld. Clinical study of a oncaa-•onth oral contraceptive t Puineatrol-Puingeatanol. Fertil. Stari1.m 110-118 (1970).
3.
study of once-e-month Larranga, A. and Berman, E. Clinical contraceptive a QuinaatrolPuingeatanol. Contraception A: 137-146 (1970).
4.
Mahall, O.R., Jr. and fraid, N.O. Life table analysis of a clinical study of a once-a-month oral steroid contraceptive : guinaatrolPuingaatanol. Contraception gr 3742 (1973).
5.
Secha, B.A. and Wolfman, L. Plasm lipid end lipoprotain changes during “Pill-a-month’ contrecaptiva steroid administration. AR. 3. Obatat. Gynac. =:155-158(1971).
6.
R., Rajandran, K.G. and Shah, U.P. Sheh, P.N., Saahadri, Acceptability, clinical effectivity and laboratory studios in Indien woman on lPill-a-month* oral contracaptives. 3. Obetat. Gynec. India 23:669475(1973).
7.
Giannina, T. and llali, A. Prolonged oeatroganic activity in rata after single oral administration of athinyloeatradiol3-cyclopentyl ether. 3. Phem. Pharmacol. a: 27%272(1969).
8.
Epstein, oeetrogan
9.
Oecia, 3-V. Book Society)
Practical Hematology 4th Edition (1969)
Frankel, S. (C.V. Aoeby
Gradwoh18e Clinical Methods Colpany ) 7th Edition (1970)
10.
238-239, 11.
J., Sobrero, A. and Rodriquaa, A.1 now oral with unusual properties. Clin. Rea. 13:241-244(1965). (The English PP 37-39
Language
and 45-46. and
Diagnosis.
PP 120-124,
258-259.
Varley, H. Practical Clinical (Interacienca Booke Inc). 4th 374-375.
JUNE 1975
R.
VOL. 11 NO. 6
Biochemistry. Edition
(1967)
PP. 82-84
and
687
CONTRACEPTION
12.
geter, S.L. Hawk’8 phySiOlOgiC81 Chamiatry. (RcGrew Hill Publishing Company Ltd ) 14th Edition 1967 pp. 1119-1121.
13.
Dunconbe, W.C. The, calorimetric microd8termination of long Chain Catty acids. Biochem. J. =:7-10
14.
Datta, C.K. and Chakrabarti, B.K. A n8w colorimatric method for the eetimation of 8erum non-esterified fatty acids. Ind. 3. fl8d. Re8. z:1309-1312 (1969).
15.
K.D. The effect of combination COnd8, u.R ., and Virkar, oral contraceptive8 and low do88 progeetogene (norge8tP81 and m8g88trOl aCetat ) On 88rUm lipids. Paper acceptrd for publication in Fertil. Steril.
16.
De Alvarez, The influence serum lipids.
R.R., of Am.
Jahed, f.fl. and Spitalny, K.3. oral contraceptive Steroid8 on J. Obetet. Cynec. 116: 727-749
(1973).
17.
Osman, R.fi., Topporada, H.K., Ghanem,, Pl.H. and Cuergir, F.K. The effect of an oral contraceptive on serum lipids. Contraception & 105-118 (1972).
18.
Harzerd, W.R., Notter, D.T., Spiger, R.3. and Si8rm8f1, E.L. Oral contraceptives and triglycsride tranepor tr Apquired heparin reaietanca a8 a mechanism for impaired poet-heparin lipolytic activity. 3. Clin. Endocrinol. Retab. 55: 425-437 (1972).
19.
Furman, R.H.,
Howard, R.P., Norcia, L.N. and Keaty, of androgens, estrogens and related 8taroid8 on s8rum lipid8 8nd lipOprOt8inS. Am. J. Med. ~:610-97 (1958). The
20.
688
(1963).
E.C.
influence
Gerahberg, He, Hulse, Il.and Javier, 2. Hypertriglyceridemia during treatment with e8trogen end Or81 COntraC8ptiVeer an alteration in hepatic function? Obstet. Cynec. 311 1660189(1968).
JUNE
1975
VOL.
11 NO. 6
U.N.Donde, Katayun
In8titutr (Indien
&SC.,
D.aGdirkac,
for
Ph.D. R.D.,
Rerearch
F.C.P.S.
in R8produotion
Council ot flodicalRsoraroh ) 38hangir Aerwnji Stre8t, Parrl, Bombay-400 012.
INDIA
ABSTRACT
Sioahonical rtudy of a long-acting oral 8t8rOid forrulation, containing 2.0 mg quin88trol and 2.5 g qUing88tanOl 8C8t8t8, WI) unckrtak8n during 8 p8riod Of 24 month8. H8moglobin, packed cell volum8, liv8r tunotion 8tUdia8 and 88rUI prOt8in8 kV8 not 8hoUA 8iQl3ifiCallt ohanQa8 while 8iQni?iC8nt inCrma888 in 88~1 triQlyo8rid88, fr88 tetty acid8, pho8pholipidr and chol88terol w8r8 ob8erved during the therapy. Th8 8lrvation in 8arum lipid8 Oaa allort ot the rimilar Mgnitudr aa ob88rv8d in daily combination pillr.
Accepted
JUNE
for
1975
publication
VOL. 11 NO. 6
April
2,
1975
681
CONTRACEPTION
Several publications have reported on the acceptability and clinical ePf icacy of quinastrolquingastancl (QQ) as a once-e-month contraceptive pill (l-4,6). However, the biochemical studies with QP are ssldor reported (5,6). Puinestrcl, i.e. sthinyl eatrsdiol 3-cyclopentyl ether, is an estrogen which has prolonged activity in animals (7) and in man (8). APtar absorption, it is stored unchsngsd in the body Pat and is released subsequently and mstsbolirsd to conjugates OP ethinyl estrsdiol. Puingeetsnol scatsts ie the 3-cyclcpentylenol ether derivative OP ncrethindrone acatate. A combination oP quinestrol and quingestanol acetate taken once-a-month has been Pound to have pregnancy rstss ot 1.9 to 0.2 per 100 women ysars (l-4,6). DurinQ our clinical trial8 ot ths once-a-•onth pill, it uas thought morthuhile to study the metabolic ePPscts and to compare them with those obtained during the therapy with the daily combination pill. The paramstsrs employed in the study were hemoglobin, packed cell volume, serum total protein, albumin, globulin, GOT, GPT, alkaline phosphatase, thymol turbidity, triglycsridea, phospholipids, tree Patty said8 and cholesterol. Thsss investigaticne mere carried out prior to ths therapy and during the therapy at epeciPic tine intervals in a group of’ Yo~n mho took the once-a-month pill (quinestrol 2.0 mu and qUinQs8tanOl acetate 2.5 ag ) tor contraception. RATERIALAN0 PKTHOOS blomen sttending Pamily plsnninp clinics attached to the Institute tar Research in Reproduction, Sombsy, were selected Por the studies. Theeo women belonpad to the lower socio-economic groups. The msan age, psrity and body wight in these women wera 26.8 + 4.8 years (range 18 to 44 years ), 3.33 + 1.7 (range 0 to-8 ) and 46.8 t4.05 kq (range 32.5 to 56.5 reopeztively.
kg),
The Pirst once-a-month pill YSS given on the 2nd day oP the menstrual cycle. The second pill ma8 given on the 22nd day of the same cycle. Thsrsstter, the pills uera given every 28th day Prom the last pill. Tha pills ware taken by the uomen in ths clinics. HsmoQlobin, packed cell volume and liver tunction studies were ot serum proteins csrriad out trom August 1971, while estimations and lipids wers started in November 1971. The csses invsstigatsd up to December 1973 are included in the study.
682
JUNE 1975
VOL. 11 NO. 6
CONTRACEPTION
The biocheaical paremeters were estimated in drawn in the morning before breakfast following 8 fasting period of at leest 12 houre. The blood sanpler heelscollscted botoro starting the therapy and r8r8 repeated after the ingoation of 6,12,18 and 24 pills. Sanplee uere analyaed for hemoglobin (9), packed cell volum8(9), asrutsGOT (lo), GPT (lo), triglycoridee (lo), phoapholipida(lO), thymol turbidity (ll), chol8eterol (ll), alkaline phosphateee(l2) and tree tatty eoids (15,14). In 66 women the pre-therapy blood eSlSp188Uere aveilable for 8nalySi8. In addition to pre-therepy valuee, the blood eamploe obtained 8t the initial Visits of the women attending family plenning clinics were 8nSly88d to obtain control balU88 for each Of the biochemicel p8rSmOtSrS. G8r8 was taken to 888 that these womn had not taken eny ateroidel contraceptive8 previously but had used conventional contraceptivee, such se condom, diaphragm, jslly, eto. A total of 240 such eampleo from women between the age group 19 years to 55 years wsre analyaad. Beaides control va1ue8, the pre-therapy value of 88Ch Caa8 8180 88rVed 88 hsr Own Control when eV8ilabl8. blood
samples
The 8tetistical evaluetion of the data for each group calculetion of the wan etanderd deviation and standard error of th8 mean. The signi?icanoe of the difference of mane use calculated by Fishorb t t88t idhileth8 SighifiOanCe O? th8 InsanOf the diffSrehC88 wee calculeted by Students' t t88t Using tuo-tail probability tablee. includsd
RESULTS
The results of the biochenical inveetigations are ahown in T8bl88 I and II. It can be seen that hemoglobin 8nd packed call volume u8r8 not eigni?icantly 8ltSred during the therapy. Similerly, there uaa no oigniticent variation in liver function tretr. Ssrun total protein8 and albumin level8 uers alightly, but not signiticently, ihor888ed during the ingestion of the pills. The results of serum lipids in 17 women who were continuously followedup for 2 years h8V8 been ahoun in Table II. There wee 8 SignifiCaht elevation in all the lipid fractions during the therspy. Serum triglycerides and phoepholipids, aftsr the ingsetion of 12 pills, uera loss than those after the intake of 6 pilla.
JUNE
1975
VOL. 11 NO. 6
683
Albumin
Globulin(gm$)
Serum
Serum
Serum A:G Ratio
Total Proteinajgmj)
Serum
(918% )
Thymcl Turbidity (Units)
Serum
1.49 ,+ 0.04
2.75 + 0.12
4.10 + 0.12
6.05 + 0.11
2.0
2.90 2 0.04
(Unite) Alkalina Phoaphataaa
Serum
1
1.20t0.03
3.16f0.13
3.72~ 0.11
6.06+ 0.10
2.3
3.15+ 0.03
0.0 + 1.15
,+ 1.10
9.0
CPT(Unite )
21.0 + 1.01
30.5 2 1.23
12.0 2 0.55
Pra-therapy (66)
2 1.63
2 1.21
Serum
19.2
37.6
12.04 ,+ 0.40
COT(Units )
1
Normal Controls (240)
Serum
Packed call volume($)
Blood HenoQlobfn (Qme d )
Eatimetion (Nuaber of Caaee )
RESULTS Of 0IOCHE~ICAL INVESTIGATIONS (lean ,+ S.E. )
TABLE I
I
1.40+0.04
2.07t0.11
4.0420.13
6.91_+0.00
2.4
3.302 0.04
9.3 + 1.25
22.1 + 1.65
40.3 2 1.03
I
1.21t0.04
3.25~0.09
3.0020.11
7.13+0.11
2.3
3.15+0.04
9.7 + 1.32
22.3 2 1.03
37.5 2 1.41
6 to 12 pills 12 to 24 pills (65) (17) I I 13.5 + 0.61 12.0 * 0.50
CONTRACEPTION
TABLE II SERIJN LIPIDS IN 17 WflfN WHO WERE CONTINUOUSLY FOLLOWED-UP FOR 2 YEARS (Flean f S.E. ).
Estimation
’
Pre-therapy
6 to
12 monthe l **
Serum Triglycerfdea(ag$)
95.63
2 2.16
75.9
2 1.00
29706
+11.12
408.6
212.11
1.35
241.5
+1.58
201.2
~6.35
13 to 24 months *eo 87.2
t
o**
l ,*o
Serum Free (A
fq/I
Fatty
Acids
1.95
407.6
+15.30
227.6
+. 2.95
) l **
Serum Phoepholipids (mg Z )
203.36+
l **
**I)
l o*
Serum Cholesterol
201 o4 +5.15
(mg Z )
we*
P
OISCUSSION The @canning of the literature revealed very feu reports (5,6) on the biochemical studio6 with GO a8 a once-emonth contraceptive pill. In our caaoa hemo#obin and packed cell volume have show no significant change8 during the therapy. This confirms the report of Sachs and Wolfmen (5) who, in a ante11 series, have shown insigniFicant rilroo in hematocrit values. The liver funotion which has been aerossed by estimating asrum GOT, GPT, alkalino phoephetaao and thymol turbidity have alro not ehoun significant changes. Thilr obeervatfon agrees with the report of Sechr, end IJolfmen(5). However, it conflicts with the report publiehed by Shah et al. (6) uho observed significant elevations in aorum CPT and’--alkaline phosphatase in uoemn taking the once-a-month pill.
JUNE 1975
VOL. 11 NO. 6
685
CONTRACEPTION
In our oasas, aarum~liplda uara 8fQniPicantly alavatad during the therapy. The rise uaa a~ora aPter the ingaation of 6 to 12 pills than aPtar 15 to 24 pills. The incraaaa in p~aama lipids and lipoproteins has bean reported by Sachs and Woltnan (5). Pravioua atudias carried out by ue (15) and others (96,17) have ahoun that, in uoaan taking daily oral combination contraceptives, the lavale oP asrum triglycaridaa, Praa f8tty acids, phoapholipida and cholesterol uara significantly elavatad. The increase in serum triglyoaridea has bean shot& to be due to fRpSir8d post-haparin lfpolytic activity. This iRpairmant is due to aoquirad haparin resistance (15). This aPPacta has been uinly attributed to the aatrogan coaponent of the pill (lg,20). The aetrogan corponant OP PO is 2.0 mg athynyl eatradiol 3ayalopantyl other which ia biologically more active then athynylaatradiol aa Giannlna and Reli (7) found that at all the doeaa tha J-ayolopantyl athar derivativa of athynyl eatradiol was mora aPtactive than athynyl aatradiol in atinulating utarina grouth. It appaara troa tha raaukta that PO combination produced aiailar ohengaa in serum lipids as reported in the caaaa taking daily combination piLla. In none of tha Eases did serum lipids axcaad tha uppar limit of normal. We found that the dropout rata in our clinics attar 12 pills uaa very high as seen by the small nua.bar oP caaaa on whom the taata uera carried out. The nonmaa 0P greater significance acceptability of this pill, tharetora, than the metabolic atfacts in the clinical trials.
ACKlmWLEOGfnK#T Tha authors aro gratatul to clinic dootora, aapacially Dr. S.S. Gikahit and Or. S.J.Kora, tar ratarring Chair ~4888. Appreciation is alas axpreaaad t0 tha social uorkara without uhoae aubatantfal motivation thia study umuld not have baan poaaibla.
686
JUNE 1975
VOL. 11 NO. 6
CONTRACEPTION
REFERENCES 1.
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