Arist. N.Z.J. Obstet. G y i i n e c . (1979) 19: 95
Prolactin Secretion During Prolonged Lactational Amenorrhoea B. A. Gross’, and C. J. Eastman2
Endocrine Unit, Woden Valley HospituI, Woden, ACT
Summury: Basal serum prolactin levels were elevated up to 66 weeks postpartum in lactating amenorrhoeic women. The serum prolactin level in fully breast-feeding women was significantly higher than in women who were partially breast-feeding. The mean basal serum prolactin level in menstruating, lactating women was significantly higher than the mean level in women who had weaned and had normal menstrual cycles. The rise in prolactin due to suckling was seen up to 66 weeks postpartum. The marked variability and lack of reproducibility of individual suckling responses may obscure the importance of prolactin secretion in the postpartum period. Nevertheless, this study confirms that prolactin secretion is increased in women with prolonged lactational amenorrhoea.
The phenomenon of lactational amenorrhoea, whereby ovulation and menstruation are suppressed while the mother is breast-feeding, is widespread among mammals (May, 1978). The duration of lactational amenorrhoea in women, however, is variable (Van Ginneken, 1974; Rosa, 1975) and full lactation delays menstruation longer than partial lactation (Perez et al., 1972; Buchanan, 1975; Gioisa, 1975). The physiological processes by which lactation inhibits reproductive activity in the human are poorly defined. I n the early postpartum period, increased prolactin secretion appears to be the most important determinant in the initiation and maintenance of lactation (Tyson et al., 1972a; Tolis et al., 1974; Bonnar et al., 1975; Rolland et al., 1975; Tyson et al., 1975, 1976). Beyond 90 days the role of prolactin is not clear. Although several reports have suggested that basal serum prolactin levels are not elevated beyond this time, (Tyson et al., l972a, 197211; Noel et al., 1974) more recent studies I. Research fellow. 2. Director.
have shown elevated levels in prolonged lactational amenorrhoea (Rolland et al., 1975; Delvoye et al., 1976, 1977a, 1978, Tyson et al., 1976; Tyson, 1977). Because the suckling induced rise in prolactin governs the initiation and maintenance of lactation in the early postpartum period (Meites, 1974), it is difficult to reconcile the data obtained from estimations of basal serum prolactin concentration with reports of absent or blunted prolactin response to suckling after the third post-partum month (Tyson et al., 1972b; 1976; Delvoye et al., 1976; Tyson, 1977). Thus, the role of prolactin in prolonged lactation and control of reproduction remains obscure. The aims of the present study were to define (a) basal serum prolactin levels in lactating amenorrhoeic women, in lactating menstruating women, and in women who had weaned their babies; and (b) the prolactin response to suckling in a sample of lactating women during prolonged lactational amenorrhoea and in a sample of menstruating women in an urban Australian population.
AUST.AND N.Z. JOURNAL OF OBSTETRICS A N D GYNAECOLOGY
96
80-
70
60
50
-
\
CI)
a.
40
f 30-
c
$ ' -I
2a 10-
13
26
39
52
65
WEEKS POSTPARTUM Figure I. Mean basal serum prolactin levels during 66 postpartum weeks in breast-feeding amenorrhoeic women, Values are expressed as mean & standard error of the mean (SEM). Horizontal broken line indicates the range for normal cycling women in this laboratory.
PATIENTS AND METHODS
Busul Studies Fifteen basal blood samples were obtained from 4 lactating mothers who had a return of 1 or more menstrual cycles, and 6 samples from mothers who had weaned and had regular menstrual cycles.
Suckfing Studies Twenty-six studies were carried out between 5 and 66 weeks postpartum on 18 volunteer lactating mothers who had given informed consent. Four mothers were studied after 1 menstrual period and the remaining mothers were studied during prolonged lactational amenorrhoea. The nursing mothers were admitted in the early morning to the clinical investigation unit and studies were performed between 10.00 a.m. and 11.30 a.m. Blood samples were obtained from an indwelling catheter inserted into an antecubital or forearm vein and samples were taken at intervals from 5 to 15
minutes before and up to 3 hours after the commencement of suckling. Every effort was made to ensure normal breast-feeding conditions and mothers were encouraged to follow their normal pattern of feeding on demand for as long as they or the baby wished at each feed. Stress effects were minimised by allowing the mothers to rest for 30 minutes after catheterisation and blood samples were taken at -30, -15 and 0 minutes before suckling began. The frequency and duration of each suckling episode was recorded. Details of menstrual status, breast-feeding status (full or partial feeding) the frequency of breast-feeding, time since last breast-feed, age and parity of the mother, and medications were recorded. No mothers were using hormonal contraceptives. Blood was allowed to clot at room temperature and the serum was separated and stored at -20°C until assayed. All samples from an individual mother were measured in the same assay. Prolactin was measured in serum samples by radioimmunoassay according to the method described by Sinha et al. (1973). The reagents VLS 3 were kindly donated by the National Pituitary Agency, National Institute or Arthritis, Metabolism and Digestive Diseases (USA). The sensitivity of the assay was 1-2ug/l with an intra-assay coefficient of variation a t 15ug/l -20%, 4Oug/1 -14%, and 120ug/I -10%. Interassay variation was 5-8%. Normal serum prolactin in nonpregnant, nonlactating women is 10.3 2 1.3 (SEM). Results were expressed in ug/I and statistical analyses of the data were conducted using Student's I tests. RESULTS
Busal Serum Proluctin Mean basal serum prolactin levels from 5 to 9 weeks postpartum, 78.5 k 15.4 ug/l (mean -+ SEM) were significantly higher (P
Prolactin Secretion During Prolonged Lactational Amenorrhoea B. A. Gross’, and C. J. Eastman2
Endocrine Unit, Woden Valley HospituI, Woden, ACT
Summury: Basal serum prolactin levels were elevated up to 66 weeks postpartum in lactating amenorrhoeic women. The serum prolactin level in fully breast-feeding women was significantly higher than in women who were partially breast-feeding. The mean basal serum prolactin level in menstruating, lactating women was significantly higher than the mean level in women who had weaned and had normal menstrual cycles. The rise in prolactin due to suckling was seen up to 66 weeks postpartum. The marked variability and lack of reproducibility of individual suckling responses may obscure the importance of prolactin secretion in the postpartum period. Nevertheless, this study confirms that prolactin secretion is increased in women with prolonged lactational amenorrhoea.
The phenomenon of lactational amenorrhoea, whereby ovulation and menstruation are suppressed while the mother is breast-feeding, is widespread among mammals (May, 1978). The duration of lactational amenorrhoea in women, however, is variable (Van Ginneken, 1974; Rosa, 1975) and full lactation delays menstruation longer than partial lactation (Perez et al., 1972; Buchanan, 1975; Gioisa, 1975). The physiological processes by which lactation inhibits reproductive activity in the human are poorly defined. I n the early postpartum period, increased prolactin secretion appears to be the most important determinant in the initiation and maintenance of lactation (Tyson et al., 1972a; Tolis et al., 1974; Bonnar et al., 1975; Rolland et al., 1975; Tyson et al., 1975, 1976). Beyond 90 days the role of prolactin is not clear. Although several reports have suggested that basal serum prolactin levels are not elevated beyond this time, (Tyson et al., l972a, 197211; Noel et al., 1974) more recent studies I. Research fellow. 2. Director.
have shown elevated levels in prolonged lactational amenorrhoea (Rolland et al., 1975; Delvoye et al., 1976, 1977a, 1978, Tyson et al., 1976; Tyson, 1977). Because the suckling induced rise in prolactin governs the initiation and maintenance of lactation in the early postpartum period (Meites, 1974), it is difficult to reconcile the data obtained from estimations of basal serum prolactin concentration with reports of absent or blunted prolactin response to suckling after the third post-partum month (Tyson et al., 1972b; 1976; Delvoye et al., 1976; Tyson, 1977). Thus, the role of prolactin in prolonged lactation and control of reproduction remains obscure. The aims of the present study were to define (a) basal serum prolactin levels in lactating amenorrhoeic women, in lactating menstruating women, and in women who had weaned their babies; and (b) the prolactin response to suckling in a sample of lactating women during prolonged lactational amenorrhoea and in a sample of menstruating women in an urban Australian population.
AUST.AND N.Z. JOURNAL OF OBSTETRICS A N D GYNAECOLOGY
96
80-
70
60
50
-
\
CI)
a.
40
f 30-
c
$ ' -I
2a 10-
13
26
39
52
65
WEEKS POSTPARTUM Figure I. Mean basal serum prolactin levels during 66 postpartum weeks in breast-feeding amenorrhoeic women, Values are expressed as mean & standard error of the mean (SEM). Horizontal broken line indicates the range for normal cycling women in this laboratory.
PATIENTS AND METHODS
Busul Studies Fifteen basal blood samples were obtained from 4 lactating mothers who had a return of 1 or more menstrual cycles, and 6 samples from mothers who had weaned and had regular menstrual cycles.
Suckfing Studies Twenty-six studies were carried out between 5 and 66 weeks postpartum on 18 volunteer lactating mothers who had given informed consent. Four mothers were studied after 1 menstrual period and the remaining mothers were studied during prolonged lactational amenorrhoea. The nursing mothers were admitted in the early morning to the clinical investigation unit and studies were performed between 10.00 a.m. and 11.30 a.m. Blood samples were obtained from an indwelling catheter inserted into an antecubital or forearm vein and samples were taken at intervals from 5 to 15
minutes before and up to 3 hours after the commencement of suckling. Every effort was made to ensure normal breast-feeding conditions and mothers were encouraged to follow their normal pattern of feeding on demand for as long as they or the baby wished at each feed. Stress effects were minimised by allowing the mothers to rest for 30 minutes after catheterisation and blood samples were taken at -30, -15 and 0 minutes before suckling began. The frequency and duration of each suckling episode was recorded. Details of menstrual status, breast-feeding status (full or partial feeding) the frequency of breast-feeding, time since last breast-feed, age and parity of the mother, and medications were recorded. No mothers were using hormonal contraceptives. Blood was allowed to clot at room temperature and the serum was separated and stored at -20°C until assayed. All samples from an individual mother were measured in the same assay. Prolactin was measured in serum samples by radioimmunoassay according to the method described by Sinha et al. (1973). The reagents VLS 3 were kindly donated by the National Pituitary Agency, National Institute or Arthritis, Metabolism and Digestive Diseases (USA). The sensitivity of the assay was 1-2ug/l with an intra-assay coefficient of variation a t 15ug/l -20%, 4Oug/1 -14%, and 120ug/I -10%. Interassay variation was 5-8%. Normal serum prolactin in nonpregnant, nonlactating women is 10.3 2 1.3 (SEM). Results were expressed in ug/I and statistical analyses of the data were conducted using Student's I tests. RESULTS
Busal Serum Proluctin Mean basal serum prolactin levels from 5 to 9 weeks postpartum, 78.5 k 15.4 ug/l (mean -+ SEM) were significantly higher (P
