Domperidone in defective and insufficient lactation

The clinical use of anti-dopaminergic drugs to stimulate plasma PRL levels, to induce lactogenesis and maintain an adequate lactation has been widely suggested, taking into consideration the main inhibitory role of hypothalamic dopamine on PRL secretion. We therefore studied the effects of domperidone (DOM), a direct anti-dopaminergic drug with a low tendency to be secreted in the milk and which does not cross the blood-brain barrier, on inducing lactogenesis in 8 puerperal women with a history of defective lactogenesis (group A) and inducing galactopoiesis in 9 puerperal women who showed 2 weeks after delivery an insufficient lactation (group B). A placebo treatment was performed in 7 and 8 puerperal women with the same characteristics of group A and B, respectively. PRL plasma levels were assayed in basal conditions and after suckling from the 2nd to the 5th day of puerperium in group A and through a 10-day treatment in group B. In both groups domperidone-treated subjects always showed baseline PRL levels and daily milk yield significantly higher than those of the placebo group (P less than 0.01). The lack of any side-effects and the positive results suggest a high usefulness of such a drug in inducing and/or maintaining successful breast feeding, which is at present considered so important for a healthy development of infants.     

Prolactin stimulation using the metoclopramide test in females taking oral contraceptives

In 31 patients taking oral contraceptives (o.c.) for a period between 1 year to more than 3 years, basal serum prolactin levels and metoclopramide induced prolactin values were determined 30 and 60 minutes following an i.v. injection of 10 mg of metoclopramide. The basal prolactin levels were elevated in 7 women to more than 1,000 mU l. The 3 groups of patients taking o.c. with different estrogen doses showed higher drug induced increase of their prolactin levels than the controls. These differences were statistically significant between groups I and III and the control group. No differences could be found between the challenged values of the users groups. The prolactin increase challenged with 200 micrograms TRH in 5 women under o.c. was considerably smaller than that observed in the metoclopramide groups, but exceeded the TRH induced levels found in the controls. The significance of these findings is discussed with special reference to the promotion of prolactinomas.     

Effect of parity on pituitary prolactin response to metoclopramide and domperidone: implications for the enhancement of lactation

OBJECTIVE: The gastrointestinal motility agents metoclopramide and domperidone are known to increase pituitary prolactin (PRL) secretion and breast milk production. This study compared the effect of single doses of two strengths of metoclopramide and a single dose of domperidone on PRL secretion. METHODS: Ten nonpregnant women had baseline evaluation of serum PRL concentrations. The PRL concentrations were then determined after random oral administration of metoclopramide 10 mg, metoclopramide 5 mg, and domperidone 10 mg. Blood samples were drawn in the first 7 days of the menstrual cycle, at 13 time points over a 6-hour period (0, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, and 360 minutes), with the zero time point beginning at 0800 hours. Variables such as weight, height, age, gravidity, parity, and oral contraceptive use were recorded. RESULTS: Baseline PRL concentrations showed the natural circadian rhythm. Metoclopramide and domperidone both caused a significant increase in PRL. However, PRL secretion was most influenced by parity. Nulliparous women had the quickest and highest PRL secretion with metoclopramide 10 mg, compared with the PRL response with metoclopramide 5 mg and domperidone 10 mg. Conversely, multiparous women had PRL secretion patterns that were equivalent between the medications. CONCLUSIONS: The PRL response to the medications was most influenced by parity. Therefore, we suggest that the medication therapy of choice for enhancing lactation may not be the same in all women, but may instead be determined by parity.     

Treatment of inadequate lactation with oral sulpiride and buccal oxytocin

Thirty-six puerperal women with inadequate lactation were treated with 50 mg sulpiride (N = 24) or placebo (N = 12) three times a day for two weeks. These treatments were supplemented with buccal oxytocin (100 IU, 300 IU, or 400 IU) or placebo preceding each breast-feeding on the sixth and 14th and on the seventh and 13th days of oral treatment, respectively. One woman treated with sulpiride and three women treated with placebo discontinued the trial because of the lack of the effect of treatment. The concentration of prolactin in maternal serum was higher (P less than .001) during sulpiride than placebo treatment at one week (380 +/- 43 ng/ml vs 23 +/- 7 ng/ml, mean +/- SE) and two weeks of treatment (381 +/- 38 ng/ml vs 34 +/- 10 ng/ml). Also, the daily breast milk yield, as measured objectively, was greater (P less than .05) during sulpiride than placebo treatment both at one week (628 +/- 51 ml vs 440 +/- 68 ml) and two weeks of treatment (684 +/- 67 ml vs 423 +/- 60 ml). Various doses of oxytocin failed to stimulate the milk secretion in the presence or absence of sulpiride-induced hyperprolactinemia. Thus, sulpiride improved inadequate lactation, whereas exogenous oxytocin alone or together with sulpiride had no effect on lactation in these mothers whose infants were able to suckle normally.     

Suppression of lactation.

Medical and psychological indications for lactation suppression are discussed, and methods for lactation suppression are evaluated. Medical indications for lactation suppression include 1) maternal anatomical abnormalities, such as inadequate secretory tissue and inverted nipples; 2) maternal breast infections and tumors; 3) the presence of certain diseases, such as tuberculosis; 4) maternal use of medications which might be harmful to the infant; 5) infant anatomical abnormalities which inhibit suckling; 6) death of the infant; and 7) a desire to wean the infant. Lactation suppression is also indicated for women, who, for a variety of psychological and social reasons, prefer not to breast-feed their infants. These women should not be coerced into breast-feeding nor should they be made to feel guilty if they opt to bottle feed their infants. Lactation suppression occurs naturally when the stimulation of suckling is absent. The drug bromocriptine, inhibits prolactin secretion and is recommended as the most effective lactational suppressant currently available. The use of estrogens to inhibit galactopoiesis is not recommended in light of the health risks associated with the use of estrogenic drugs.     

Endocrinology of lactation.

Hormones are necessary for the growth of mammary glands, for initiation of the secretory process, and for the maintenance of an established lactation in all mammals. Hormonal changes which occur in late pregnancy and the early postpartum period are described and graphed. This data was derived from research with animal models and relevant human data. Enzymatic and cytologic differentiation of the mammary gland and limited mammary secretion begin during late pregnancy. This constitutes the 1st stage of lactogenesis. The 2nd stage consists of a great increase in lactation secretion occurring 0-4 days before delivery. Quantities of milk produced are very variable. The role of all the following hormones in lactogenesis are described: prolactin; adrenocorticotropin (ACTH, which stimulates glucocorticoid secretion); estrogens; placental lactogens. Maintenance of intense lactation also depends on a complex of hormones. Prolactin seems to be the most important hormone at this stage of the process. Milk secretion continuation is reliant on constant milk removal.     

Suppression of puerperal lactation by terguride. A double-blind study

Clinical efficacy, prolactin (PRL)-lowering effect and tolerance of terguride (an 8-alpha-ergoline derived from Lisuride which acts as a partial dopaminergic agonist) were investigated in a double-blind study on inhibition of puerperal lactation using three different daily doses of the drug (0.25, 0.5 and 1.0 mg). With 0.5 and 1.0 daily therapeutical regimens PRL levels were suppressed in a dose-dependent manner and lactation was prevented. Terguride was highly well tolerated.     

Drugs affecting lactation.

The effects of a variety of drugs on lactation are described. Drugs affect lactation either by modifying breast tissue or by influencing prolactin secretion. Androgens and progesterones stimulate the growth of breast tissue, and estrogens, which are frequently used to suppress lactation, stimulate breast duct growth. Many psychotropic drugs increase prolactin levels and cause galactorrhea while other centrally acting drugs inhibit lactation. The names and the mechanism of action of all centrally acting drugs which cause galactorrhea and of all those known to inhibit lactation are provided in tabular form. Suggestions related to the clinical use of the sex steroids and the centrally acting drugs are 1) the use of estrogens to suppress lactation should be limited to the shortest possible time; 2) if galactorrhea occurs in a menopausal patient who is taking oral contraceptives or estrogens, she should be examined for pituitary tumor; 3) if galactorrhea occurs in a patient who is taking a centrally acting drug known to cause galactorrhea, the patient need not be examined for pituitary tumor unless other symptoms are present; 4) the use of centrally acting drugs by women predisposed to breast cancer should be avoided; 5) nursing mothers should avoid taking large doses of barbiturates and pyridoxine as these drugs may reduce lactation; and 6) the use of bromocryptine to suppress postpartum lactation may stimulate early ovulation, and patients should be warned about the need to use contraceptives.     

Improvement in timing of antibiotic administration by using a prophylactic antibiotic record form.

BACKGROUND/PURPOSE: To evaluate the effect of a form recording the timing of prophylactic antibiotic administration, antibiotics used, and treatment duration on the proper use of prophylactic antibiotics in patients undergoing four types of operations. METHODS: This was a retrospective study in a 682-bed, university-affiliated, tertiary teaching hospital. Using the form developed, nurse practitioners recorded the timing of prophylactic antibiotic administration, antibiotics used, and treatment duration for patients undergoing three types of clean operations (total hip replacement, total knee replacement, thyroidectomy) and one type of clean-contaminated operation (hemorrhoidectomy). Patient records were identified by chart review after searching the hospital database. A case was defined by a principal or secondary procedure code for the four types of operations. Patients who received therapeutic antibiotics for documented preoperative infection were excluded. RESULTS: A significant improvement (p<0.001; OR, 33.768; 95% CI, 4.304-264.951) in the use of prophylactic antibiotics was noted between the pre-intervention and intervention periods. Among the three criteria of antibiotic usage, the improvement in the appropriate timing of prophylactic antibiotics was significant (p<0.001; OR, 46.247; 95% CI, 5.891-363). The accuracy of the prophylactic antibiotic form in recording the timing of antibiotic administration, the choice of antibiotics, and the treatment duration was 84.2% (16/19), 89.4% (17/19), and 100% (19/19), respectively. CONCLUSION: The prophylactic antibiotic form effectively decreased the inappropriate use of prophylactic antibiotics. Due to its high degree of reliability, this infection control measure can be used as a continuous monitoring system for prophylactic antibiotic use.     

Home subcutaneous metoclopramide therapy for hyperemesis gravidarum.

OBJECTIVE: To describe the use of subcutaneous (s.c.) metoclopramide in the outpatient treatment of hyperemesis gravidarum. STUDY DESIGN: In a retrospective design, women who received continuous s.c. metoclopramide for treatment of hyperemesis gravidarum were identified from a national database. Data analysis included weight at start and stop of treatment, frequency of resolution of symptoms, and side effects of medication. In addition, data were collected on adjuvant therapies. RESULTS: Between January and December of 1997, there were 646 women with hyperemesis gravidarum who received continuous s.c. metoclopramide on an outpatient basis. A total of 413 patients (63.9%) had complete resolution of symptoms. Seventy-five percent of patients had received one or more antiemetic medications before initiation of s.c. metoclopramide. A total of 192 patients (30.5%) reported at least one side effect related to treatment. The majority of reported side effects were considered mild and did not require discontinuation of s.c. metoclopramide. CONCLUSION: S.c. metoclopramide appears to be a safe, effective treatment for hyperemesis gravidarum. Outpatient treatment may result in decreased costs compared with inpatient hospitalization.     

Differential prolactin response to oral metoclopramide in nulliparous versus parous women throughout the menstrual cycle

OBJECTIVE: To analyze if serum prolactin (PRL) changed throughout the menstrual cycle and if parous women have lower PRL than nulliparous women. DESIGN: A prospective study of PRL was performed in basal conditions and during oral metoclopramide stimulation on days 7, 14, and 21 of menstrual cycle. SETTING: Instituto Nacional de Perinatología, third level medical institution. PATIENTS: Four parous (group A) and seven nulliparous (group B) healthy volunteer women entered and finished the study. INTERVENTIONS: Women were studied each day before and every 30 minutes during 2 hours after oral metoclopramide (10 mg). MAIN OUTCOME MEASURE: Duplicate PRL determinations were performed by radioimmunoanalysis. Hypothesis was formulated before data collection. RESULTS: Group A and B had similar basal PRL levels and no within group differences existed in response to metoclopramide, regardless of the day studied. Group A had lower PRL increments than group B from 60 to 120 minutes on days 14 and 21 (P less than 0.05); the peak increments also were lower on days 7, 14, and 21 (P less than 0.05). CONCLUSIONS: Parous women had a diminished PRL response. Although the dopaminergic tone was similar throughout the menstrual cycle within each group, two distinct levels of dopaminergic tone existed in parous and nulliparous women.     

Suppression of puerperal lactation by metergoline

Suppression of puerperal lactation by a potent serotonin antagonist, metergoline was studied in 33 puerperal women, i.e., abortion after sixteen weeks of gestation 6, premature labor 13, labor at term 13, and hydatiform mole 1. The drug was administered orally at a dose of 4 mg bid for 5 days to 26 subjects, starting within one week from delivery (group A). The remaining 7 subjects received 4 mg of metergoline bid for 7 days after more than 2 weeks from delivery (group B). Lactation was either rapidly suppressed or prevented in 22 out of the 26 subjects in group A and in all subjects in group B. After the therapy was stopped, rebound phenomena were observed in 4 subjects in group A and in 2 subjects in group B, but a further 5-7 days' treatment with metergoline produced satisfactory results. The mean plasma prolactin levels, studied in 10 subjects in group A at hourly intervals after the first metergoline dose, decreased significantly one hour later (p less than 0.05) and reached the nadir level, 19.9 +/- 2.6% of the mean basal value, 4 hours later. The daily plasma prolactin levels in 9 subjects were significantly lower than those of the control group during metergoline treatment (p less than 0.001). No side effects of metergoline medication were observed. Metergoline for a short course of administration is very effective in the suppression of puerperal lactation. In case of the suppression of lactation after the second week of puerperium, 10-14 days of metergoline treatment is recommended to avoid the rebound phenomena.     

Studies on the modification of puerperal lactation using methylergobrevin

During the first 6 days after delivery the daily amount of mild secretion was measured in 300 nursing puerperae who had been treated with 0,2 mg of Methylergobrevin per day in combination with 100 IU Oxytocin. The milk let-down was compared with that of 300 untreated puerperae nursing under the same conditions. A significantly smaller milk let-down was found in treated old primiparae over 30 years, multiparae between 19-30 years and puerperae after premature delivery. In puerperae desiring to nurse their babies the routine post-partum treatment with Methylergobrevin should always be combined with Oxytocin. In women who had a premature delivery and in old primiparae a postpartum treatment with Methylergobrevin should be avoided.     

Effect of a combined oral contraceptive on lactation and growth of the infant

This work describes a study conducted in a University of Chile hospital to determine the influence of a combined oral contraceptive (OC) containing 30 mcg of ethinyl estradiol and 150 mcg of norgestrel on lactation and infant growth. 103 women exclusively breastfeeding began using the OC on day 30-35 postpartum, 59 women exclusively breastfeeding whose infants gained at least 20 gm daily during the 3rd month of life began using the OC on day 90 postpartum, and 109 women exclusively breastfeeding received an injectable placebo on day 30 postpartum and an IUD or spermicides on day 90 if desired. A subgroup of 82 women from the 30-day control group who continued breastfeeding exclusively at day 90 postpartum and whose infants gained at least 20 gm daily during the 3rd month were a control group for the women beginning OCs on day 90. Follow-up visits were arranged every 10 days through the 3rd month and every 30 days subsequently through 1 year. At the beginning of the study, treatment and control groups were similar in age, parity, weight, maternal hemoglobin, and sex and weight of infants. 63 women were excluded from the study while still breastfeeding for a variety of reasons including loss to follow-up. The main reason for exclusion of OC users was termination of OC use or change of method. 11 pregnancies occurred in controls using spermicides or no contraception. Among women using OCs starting at day 30 postpartum, the percentage exclusively breastfeeding was significantly lower than among controls beginning in the 4th month, and a higher percentage of cases gave supplementary feedings on the advice of their physicians or their own decision. At 6 months, 61% of controls and 40% beginning OC use at 30 days were still breastfeeding exclusively. Fewer women beginning OC use at 90 days than controls were exclusively breastfeeding at 6 months, and a higher proportion were giving supplementary feedings on medical advice. The 2 treatment groups had smaller weight gains than their control groups in the 1st month of treatment. Total weight gain to the 6th month was significantly different for babies whose mothers began OC use at 30 days but not for those beginning use at 90 days. The average absolute weight of infants in the groups beginning treatment at 30 days was significantly lower at several ages but the differences were small. Growth of infants was good in most cases. Only 6 presented significant intercurrent illnesses. There were no deaths. No pregnancies occurred in women using OCs and tolerance was good. 1 woman discontinued use for metrorrhagia. It was concluded that the OC tested moderately inhibits lactation, especially when use is begun at the beginning of the 2nd postpartum month.