C O N T R A C E I O N
FE ILl R U TI IN NURSl W N. VI. Contracept e Effect eness of a Subde al Progesterone plant
S. Dfaz, O. Peralta, G. Juez, C. Herreros, M.E. Casado, A.M. Sal tlerra, P. Mira a a~ H.B. Cro t to
NSU ORIO P IFIC ION F ILIAR Centro National de la F ilia J.V. Lastarria 29 - Depto. I01
Santiago, I
ABST T
Six progesterone pellets implanted subdermally were tested as
contraceptive t d for lactating men. One pregnancy s diagnosed in 1614
w an- nths of observation, a failure rate which s s ilar that obse~ed
in a contemporary group of Copper T users. Nineteen pregnancies were
diagnosed in the 677 w an- nths obse ed in trea=ed iactati en. The
progesterone implants re effective en administered either at 30, 60 or 240
days after delivery. The duration of the effective llfe s 5 nths and
fertility s quickly restored after rds. There re no delete ous effects
u n maternal or i ant health or u n lactation and the rate of child gr th.
The main problem encountered s the occurrence of pellet expulsion at a
vari le rate ich ap ared related to the ma fact i procedure.
Submitted for publication Septe er 12, 1984 Accepted for publication Septe er 17, 1984
BER 1984 VOI.,. 30 NO. 4 311
C O N T R A C E P T I O N
INT DU ION
The inhibition of fertility associated with breastfeedl is highly
riable a ng individuals and tends to decrease as time elapses following
delivery. This fact dete ines the need for contraceptives that can be used
duri lactation thout interfering th milk production or child health (I,
2, 3)-
In previous p lications (4, 5) discussed the tential ad ntages
of using the natural hot ne, progesterone, as a contraceptive during
breastfeedl a the ellmlna results obtained with a s de al plant of
six o sterone pellets re re tied° is paper gives an updated account
of the contraceptive effect eness of ogesterone ministered by this means
and discusses the observed ad ntage8 of such a thod.
E D THODS
p~ation: Vol teers enrolled in the study re selected fr a healthy
postpartum en o met the Ii requlr ents: ages 18 to 35, parity 1
to 3, no a! e ancy and vaginal te delivery of a healthy infant with a
birth weight adequate to the gestatlonal age. They had to be regularly
c blti , free fr drug t ra and willing to rse their infants as long
as s s!ble.
Selectlon was done at the maternity rd ere instructions on the
tec ique of breastfeedl on de nd re gi n. ditional requirements at
the time of initiati treatment re no al postpart evolution, no al
physical e inatlon of ther and ild, h oglobin values higher than I0 g%
and a normal nutritional state. All cases re required to be in c sire
breastfeedl th an adeq te infant growth rate before admission.
Treatments: Progesterone was administered by subde al insertion of s
progesterone pellets. Contemporary control groups were fo ed by women
treated th an IUD or a placebo injection. The allocation to an injectable
met d or an IUD s at tlent olce.
- Progesterone pellets: Pellets were made by c esslng I00 of the
312 OC R 19 V O L 30 NO. 4
C O N T R A C E I O N
steroid into a cylinder of approxi rely 11.8 mm length by 3.2 mm diameter.
Three different batches (I, II and III)were manufact ed usl different
te niques. C pression s applied along the Longitudinal axis in batches II
and III and perpendicular to it in batch I. The progesterone used was
p dered in t es I and II and precompressed in batch III. Each subject
received 6 esterone llets that re inserted s de ally in the gluteal
region t ough a No. 9 gauge trocar under local anesthesia. Insertion of
pellets was done at day 30 or 60 after delivery. Pellets re petted to
ha an effecti life of 5 or 6 nths. cordingly, wo n o re treated
at day 60 were offered a second set of pellets at approximately day 240
post rtum provided they re still nursing their babies.
- Intrauterine device: The IUD used in this study s t Copper T 2 0 0
(supplied by the Asociaci6n Chilena de Protecci6n de la F illa). It s
inserted at d 30 or 60 postpartum to match the contemporary groups using
pr esterone llets.
- Placebo: The placebo consisted of an injection of 3 of distilled
ter, offered as a test treatment to sustain lactation and therefore to
support the fertility inhibition associated with breastfeeding. Women
enrolled in this group re offered non-hormonal contraceptives at the 6th
postpartum month or earlier if suppl entary bottle fe~i s introduced.
The placebo was administered at day 30 postpartum. This group was
disconti ed en it bee ident that full rsl alone or rtial rsl
supple nted th rrler t ds ovlded poor protection (6).
Follow- : Follow-up s designed to dete ine the occurrence of egnancy,
breastfeeding perfo ante, i ant gr th, s~e effects a bleedl pattern.
Visits re scheduled at nt y intervals up to the sixth postpart month and
at two-month inte als =hereafter. At each visit, the mater I a infant
h i s t o r i e s r e r e c o r d e d a b o t h t h e r a i l d r e e x a n e d . B r e a s t f e e d i
perfo ante a i ant gr h re carefully I ted usl the Boston curve
f o r b o y s ( 7 ) a s =he r e f e r e n c e s t a n d a . S p e c i a l c a l e n d a r s r e d i s t r i b u t e d t o
r e c o r d a l l b l e e d i a s t t i y s a n d t h e e r o f b r e a s t f e e d i e p i s o d e s
p e r d a y .
P r e g n a n c i e s w e r e d i a g n o s e d b y c l i n i c a l e x a m i n a t i o n a n d u r i n a r y
ER 19 VOL. 30 NO. 4 313
C O N T R A C E I O N
unologleal tests for H . Pregnancy tests ;were performed when menses were
delayed for 20 days or mote, en enorrhelc w en reached the 6th stpart
month and before the insertion of a second set of progesterone pellets at day
240 after dellvery.
P r o g e s t e r o e ........ b l o o d ........... l e, v e l s : B l o o d s p l e s r e d r n a t 1 0 - o r ! 5 - d a y i n t e ~ a l s
fr a subsample of users of the 3 different batches of progesterone pellets
during the first segment of use and from control subjects. Progesterone
levels re dete~ined by R as iously described (8) usi the procedures
a reagents provided by the Programme for the Provision of Matched Assay
Reagents for the RIA of Hormones in Reproductive Physiology of the World
Health Organization.
Dat~a anal sls: The month of conception s est ated by adding 14 days to the
first day of the last bleeding run observed. It s confl ed or adjusted
when possible by reference to the esti ted gestational age of the neonate.
The Pearl Index was used to est te the o bility of pregnancy at various
inte Is during treat nt.
L_actatlon was classified up to the 6th month of age as full nursi or
exclusive breastfeedl if the breast s the only source of nutrients for the
:baby. After the 6th month, non-dalry food was prescribed routinely and
lactation s still classified as full nursing if the breast was the only
source of milk. The proportion of cases remaining in the full nursing
condition was used to assess the effect of treatment upon lactation.
Supplement was prescribed by the pediatrician when the rate of infant growth
indicated inadequate milk supply. In se ral cases, the supplement was self-
prescribed by the mother based upon her subjective evaluation of milk
production and child satisfaction.
The occurrence of severe interc!irrent disease, prolo ed or repeated
separation of mother and child, discontinuation of treatment or
los t-to-follo~up dete~ined cluslon of the case fr analysis o~ lactation
and infant gro h follo-w~,ng the la3t visit prior to the event.
~In order to assess the effect of treatment upon in~ant growth, the
rage absolute ight at each nth of llfe and the rage Ight increase
314 R 19 V 30 4
C O N T R A C E I O N
at monthly and daily intervals re calculated for each group. Only cases in
exclusive breastfeedl were included. Calculations re done up to the 8th
month of age.
The occurrence of uncomfortable or prolo ed bleedl was analyzed
through the proportion of n o experienced re than 6 days of bleeding
plus spottl per 30-day inte~al after trea ent.
Contingency table analysis and student's "t" test were used to assess
the statistical significance of differences in distribution and mean values,
respectively. 0nly p values <0.05 re considered significant.
~SULTS
The number of subjects enrolled in each treatment group is sh~n in
Table I. Ninety-two out of I12 women (82.1%) accepted the relnsertion of
progesterone pellets that was offered at day 240 ~stpartum.
The plasma progesterone levels achieved ~th the 3 different batches
of pellets are show~n in Figure i. They reached their ~xlmum within ten days
of insertion and declined gradually thereafter remaining elevated at least for
5 months in comparison to the control group. Levels obtained with the 3
batches were of slmilar magnitude.
The local tolerance to progesterone pellets was poor. Expulsion
occurred in 2.4% of subjects from batch I, in 31.7% of subjects from batch II
and in 9.9% of subjects from batch Ill. ~e t e elapsed between insertion
and expulsion varied from several days to five months.
Table II shows the occurrence of pregnancy in women treated with
progesterone pellets according to the breastfeeding status and the time of
treatment. This table includes only the first 5 months after each
progesterone plant insertion. For this reason, the 8th postpartum month is
not included. No pregnancies re obse~.,ed in the first 5 nths of urea ent
in full nursing women when treatment was given at day 30, 60 or 240
postpartum. Only one pregnancy s diagnosed in rtlally nursl w~en and
it occurred in the 4th month after insertion. The overall incidence of
pregnancy was I in 1614 months. This figure is c table to the fertility
inhibition obtained w~th the Copper T in the s postpart intervals. Both
treatment groups showed a significantly lower incidence of pregnancy as
O-CToBER 1 9 8 4 VOL. 3 0 NO. 4 3 1 5
C O N T R A C E I O N
I
Distribution of Subjects Accordl to Trea nt
and Day of inistration
Initiation of Trea ent No. of S Jeers Postpart D
Progesterone Pellets
D 30 : Batch !
Day 60: Earth II
Batch III
Day 240: tch Ill
84
41
152
92
Copper T
30
D 60
125
121
Placebo
D 30 130
316 R 19 VOL. 30 NO. 4
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ng/ml
6 o
m
a
~Im
a
O
Q Batch I
Batch II
0 Batch Ill
4 . on, o
, , , * ÷ ¢, • o * •
......... -~-- ~ °~'T =--~ .... :-i .............. ~. .............................. , ...... , ............................... . ........ = i .... ~ .... -, ..... - ..... , ....... ........ l ............. ...................... --= . ....... -, ..... . ..... .............
0 30 60 90 120 150
T R E A T M E N T DAYS
Fig. i" Plasma progesterone levels (X + S.E.) in lactati w en treated
th progesterone pellets from Batch I ([~), Batch II (~) and
Batch III (o) and in control cases (e).
B E R 1 9 V O L 3 0 N O . 4 3 1 7
C O N T R A C E ION
BLE II
Contraceptive Effectiveness of Progesterone Pellets versus Copper T and
Placebo cording to the Breastfe i Status and the Obsereatlon Period
Treatment Breastfeeding No. Pregnancies / No. man-months Status Ohse~,,a tlon Period*
( Po 8 t pa r t Hon th s )
2 - 68 3 - 7h 9 13c TOT
Progesterone Pellets
clus e 0/339 0/594 0/144 Supple nted 0/17 I1199 0/205 Wean 0 / 1 0 0/37 0/69
1 0 / 3 6 6 1 / 8 3 0 0, /418 ~/16!4
Copper T clusive 1/471 0/420 1/252 Supple nted 0/43 0/164 0/268 Weaned - 0/'39 0/72
1 1 / 5 1 4 0 / 6 2 3 1 / 5 9 2 2/1,729
Placebo a Exclus e 91502 - 1/49
Sup pleme n ted 4 / 49 - 5/77 Wean - - -
l i3/551 - 6/126 t9/677
* 13, the first five nths postpartum ~IIo ng insertion were considered el e this is the eat ated effective llfe of progesterone plants (See Tab le II I).
a Treatment Inltlat at day 30 ~stpart .
b Trea ent initiated at day 60 postpart . c Trea nt initiated at day 240 post rt in progesterone pellets gr p
and at day 30 or 60 in the oEher o groups. d S e men used s £clde8 ~fter the sixthpostpart n~h.
3 1 8 BER 19 VOL. 30 NO. 4
N T R A C E ION
compared to the place gr p in i 19 pregnancies ~ere diagnosed in the
6 7 7 a nthe o b s e ed in c par le st rtum inte is.
Table III shows the overall contraceptlve effectiveness of six
progesterone pellets for different treatment le ths, regardless of the
ti of insertion. Treatment was hlghly effective during the first five
months of use. The effectiveness decreased en t obse tlon s extended
to nth8 6 and 7 ere 3 and 6 pregnancle8 w~re dla~nosed i~ 239 and 72
W n-months of expos e , respect ely.
The cumulates distribution of n co ~ng to their breastfeedi
status at the 6th postpart nth is sho in Table IV. Treatment groups
~nltlated a~ day 30 or 60 st rt h breastfeedi evolutions s ilar to
thelr coat orary ntrol gr ps. Both serie~ initiated at day 60 showed a
higher proportion of su 1 eared cases ~t e 6th n c pared to the
series started at day 30.
The gr th of elusively breastfed ~nf~ts s s ilar In treated and
control groups en analyzed through the averase absolute body Ight at each
nth of age and the aver e mont y a daily Ight inc ass. Table V s
the average ight crease of 8 ely breastfed i ants ~ fr birth to the
6th month of age. Values fo~ all groups were within the normal range
according t o the standard used f comparlson.
No m~Jor side effects re detected. The bleedlnH pattern sh ed
disruption during the first month of use of pellets comparable to =hat
obse~ed after ~nsertlon a Copper T. ble VI sho the proportion of full
nursing ~ w e erienced 6 or re d s of b edln~ p s spotting per 30-
day inte al. cessna bleedi s infrequent in all gr ps after the first
n of treat nt. tar the insertion of the secon~ set of implants at day
240 postpartum, the proportion of women who reported more than 6 days of
bleedln E per interval ranged fr 6Z (third nth of treatment) to 16Z (flfth
month). In t sa ~rlod, the oportlon of Cop r T use o experienced
re than 6 d s of bleeding ran d fr 21~ to 31%.
DIS SSION
The results of this st y s w that the cont~ ous mln~stration of
progesterone by ans of an ~mplant i ibits fertility in lactatlng women and
BER 1984 VOL. 30 NO. 4 .t19
C O N T R A C E I O N
TA E III
Duration of t h e Contracept e Effectiveness of S!x Progesterone Pellets
Months of Pregnancies/ Pearl Treatment Wo nths Index
1 t o 5 ! / 1 6 1 4 0 . 7 4
6 3 / 2 3 9 1 5 . 1
7 6 / 7 2 I 0 0 . 0
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TABLE IV
C ulatlve Distribution of en Accordlr~ to their
Breastfeedi~ Condition at the 6th Postpartum Month
A NT Insertion
(Postpartum day)
Excluslve U s e of Supplementa~ Feedi Breastfeeding dical ternal
Prescriptlon Decislon z Z z
Progesterone
Pellets 30 73 68 21 11
60* 127 53 39 7
Cop~r T 30 106 60 29 11
60 105 50 36 14
Placebo 30 105 71 26 3
N ffi N er of cases observed at day 180.
* ~ses treated w~th pellets from Batch II ~re excluded because of the
bias introduced by the high nu er of expulsions.
OC BER 19 VOL. 30 NO. 4 321
C O N T R A C E P T I O N
TABLE V
erage Weight Increase of Exclus~.,ely Breastfed Infants
from Birth to the 6th Month of Age
Initiation of Treatment N ~~ght Increase (g) (Post rt Days) X + S.D.
Progesterone Pellets
Day 30
Day 60
46 4515 + 621
60 4730 + 670
Copper T
Day 30
Day 60
64 4801 + 817
49 4798 + 546
Placebo
Day 30 68 4663 + 529
3 2 2 BER 19 VOL. 3 0 NO. 4
C O N T R A C E I O N
BLE Vl
Percentage of Full Nursi Women who Experienced More than 6 Days
of Bleedlng or Spotti per 30-Day Inte~al
te al (Postpart Progesterone Pellets Copper T Placebo
days ) 30* 60* 30* 60* 30*
31 - 60 46 - 52 - 22
61 - 90 12 18 10 30 4
9 1 - 120 8 5 14 16 5
121 - 150 6 5 12 15 8
151 - 180 9 4 17 15 7
* Postpart day of insertion.
BER 19 VOL. 30 NO. 4 323
C O N T R A C E I O N
t h a t i t c a n b e u s e d f o r c o n t r a c e p t i p u r p o s e s , e p r e g n a n c y r a t e o b s e r v e d
during the period of elevated plasma levels of the steroid is highly
satisfactory and thin the ran of a Copper T IUD. The high incidence of
pregnancies observed in the placebo group all s the conc slon that the 1
fertility of the treated groups was not determined exclusively by
breastfeedi .
The duration of elevated plasma progesterone levels and of an
acceptable contraceptive efficacy s limited to 5 nths. After this period,
fertility was quickly restored as can be inferred from the number of
preg ncles observed at the 6th and 7th nth after insertion, is led us to
offer a second set of Implants after the haustlon of the first rese olr to
wo n o re still iactati at t t tl . 1 incidence of egnancies
observed in the second segment is reassuring of the contraceptive
effectl ness of progesterone plants during lactation and shows that its
efficacy applies also to io -te lactation.
e use of progesterone ind ed no ad rse side effects on lactation
as judged by the ortion of cases in clus e breastfeedlng a the gr th
rate of exclusively breastfed infants up to the 6th postpartum month.
Treatment with progesterone pellets or a Copper T resulted in a higher
proportion of subjects who experienced more than 6 days of bleeding as
c pared to t treat n. eft less, this s a transient obl ,
limited to the postlnsertlon period and did not represent a reason for
discontinuation or a health risk for the s jeers, deleter s effects
upon Inf t health re detected.
The percentage of women who were willing to use a second set of
progesterone plants indicates that this is a Ii accepted alternatl .
The main problem encountered during this experience was the high
incidence of expulsion of the progesterone pellets Ich appears to be
partially related to the manufacturing technique. The results reported
justify n efforts to d el an o d st r the long-term delivery
of ogestero .
3 OC R 19 V O L 30 NO. 4
C O N T R A C E I O N
A EDGE NTS
The authors are grateful to the authorities of the Hospital Paula
Jaraquemada and the Central Health Area of Santiago for the facilities
provided for this study, to the Instituto Bioqufmlco Beta for the provision of
progesterone pellets, to the 0 Progra for the Provision of tched Assay
Reagents for the RIA of Hormones in Reproductive Physiology, and to the
International Develo nt Research Centre of Canada and to the International
Committee for Contraception Research of The Population Council for their
support.
FE NCES
I e
0
O
I
O
O
0
0
Van Ginneken, J.K. The chance of conception during lactation. J Biosoc
Sci, Supp 4-41-54 (1977).
Lau ran, V.H. Contraceptive choices for lactating women" suggestions for
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McCann, M.F., Liskin, L.S., Piotrow, P.T., Rinehart, W. and Fox, G. La
lactancia materna, la fecundidad y la planlfleaci6n familiar.
Population Reports J 24, October 1982.
Croxatto, H.B. , D~az, S. , Peralta, O. , Juez, G. , Casado, M.E.,
Salvatlerra, A.M. and Dur~n E. Fertility regulation in nursing women.
II. Comparative perfo nee of progesterone implants versus placebo and
Copper T. J Obstet G ecol 144:201-208 (1982).
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M.E., Salvatlerra, A.M. and randa P. Subdermal progesterone implants
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D~az , S. , Peralta, O., Juez, G., Salvatierra, A.M., Casado, M.E.,
Dur~n, E. and Croxatto, H.B. Fertility regulation in nursing women. I.
e probability of conception in full nursing ~omen living in an urban
setti . J Biosoc Scl 14 -329-341 (1982).
Nelson, W.E., Editor. Textbook of Pediatrics, 8 ed. W.B. Saunders Co.,
Philadelphia P.A., 1964. p. 42.
Croxatto, H.B., DKaz, S., Peralta, O., Sal tlerra, A.M. and Brandeis,
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OCTOBER 1984 VOL. 3 0 NO. 4 3 2 5
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