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Biomedical subjects

H J Bennink

Publications and source records attributed to H J Bennink.

At least 19 recordsLinked to original sources
PubMed2001

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women.

OBJECTIVE: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. METHODS: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17beta-estradiol/desogestrel (17beta-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43-58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17beta-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. RESULTS: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17beta-E-D: -7.8% and CEE-N: -8.4%) and lipoprotein(a) (17beta-E-D: -11.7% and CEE-N: -28.3%) were found compared to placebo. Apolipoprotein A1 (17beta-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17beta-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. CONCLUSION: Treatment of perimenopausal and early postmenopausal women with 17beta-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.

Adult↗
PubMed2001

Lowering of HDL cholesterol in post-menopausal women by tibolone is not associated with changes in cholesterol efflux capacity or paraoxonase activity.

Low HDL cholesterol increases the risk of coronary heart disease. Treatment of postmenopausal women with tibolone lowers HDL cholesterol. We elucidated the consequences of this unwanted side effect in a randomized, double-blind study, where 12 women received 2.5 mg tibolone per day and 6 women, placebo. Blood samples were collected on days -1 (i.e. baseline), 28, 56, and 84 for the analysis of various parameters of lipid metabolism and HDL function. Compared to placebo, treatment with tibolone led to statistically significant decreases of HDL cholesterol (-22% to -32%), apoA-I (-14% to -22%), and HDL subclass LpA-I (-30% to -40%) but to no significant changes in apoA-II and HDL subclass LpA-I,A-II. These changes were not associated with statistically significant changes in the activity of plasma to release 3H-cholesterol from radiolabeled fibroblasts or in the serum activity of the anti-oxidative enzyme paraoxonase/arylesterase. There were no significant changes in either serum levels of triglycerides, LDL cholesterol, apoB, and leptin, or in LDL size. We conclude that changes in insulin do not contribute to the lowering of HDL cholesterol by tibolone. Despite decreased HDL cholesterol, putatively anti-atherogenic activities of HDL remained unchanged.

Aged↗
PubMed2001

Tibolone and its effects on bone: a review.

This review examines the evidence for the effects of tibolone on bone. Tibolone is a synthetic steroid with a mixed (estrogenic-progestogenic-androgenic) hormonal profile. Data suggest a complex receptor-mediated as well as metabolic regulation of the activity of tibolone at target tissue level. It has been shown that tibolone can prevent axial and appendicular bone loss induced by ovariectomy and/or a low calcium diet in young and mature rats. In addition, tibolone increases trabecular and cortical bone mineral density in rats with established osteopenia. In the rat, treatment with tibolone results in an increased strength of the femoral neck and of the vertebral body, similar to that found with estrogens. The protective effect on bone can be blocked by antiestrogens, indicating that the effect is estrogen receptor-mediated. Clinical trials have shown that loss of bone in the spine and proximal hip can be prevented with tibolone 2.5 mg/day in early- and late-postmenopausal women. In addition, a dose of 1.25 mg/day seems also to be effective, especially in late-postmenopausal women. In women with established osteoporosis, bone density of the axial and appendicular skeleton increases with tibolone. In comparative studies, tibolone 2.5 mg/day seems to be as effective as conventional hormone replacement therapy regimens. There are no direct comparative studies between tibolone and bisphosphonates or raloxifene. Furthermore, to establish the efficacy of tibolone for prevention of osteoporotic fractures, studies of the magnitude of reduction in fracture risk remain to be conducted. Finally, tibolone seems to be effective in preserving bone density in patients treated with gonadotropin-releasing hormone agonist.

Anabolic Agents↗
PubMed2000

Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women.

OBJECTIVE: To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial(R)). METHODS: A 2-year randomised placebo-controlled study of 94 healthy women, 1-3 years after spontaneous menopause, receiving either placebo (n=23), 1.25 mg/day (n=36) or 2.5 mg/day (n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage. RESULTS: Fifty-one percent (n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% (n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% (n=5) in the placebo group. The women who bled in the placebo group were younger (P<0.01), had menopause at an earlier age (P<0.05), had a shorter duration since menopause (P<0.05) and had a higher median E2 serum level prior to bleeding (P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation. CONCLUSIONS: In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2-2.5 times more likely to present with vaginal bleeding compared with placebo (P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.

Bone Density↗
PubMed2000

Effect of Implanon use on selected parameters of thyroid and adrenal function.

In this article, the effects of Implanon implant use on thyroid and adrenal function was compared with those of Norplant implants. In this 2-year open randomized study of 80 implant acceptors, we found that both implants may induce minimal changes in thyroid hormones and cortisol levels, possibly secondary to alterations in the respective binding globulins in the serum. These alterations in thyroid and adrenal function would have no clinical significance in healthy women. In the Norplant group, sex hormone-binding globulin levels decreased, whereas increased levels were found in the Implanon users at the end of 2 years. These findings lend support to the fact that etonogestrel, released from Implanon implants, is significantly less androgenic than levonorgestrel, released from the Norplant implants.

Adrenal Cortex↗
PubMed2000

The pharmacokinetics and pharmacodynamics of Implanon, a single-rod etonogestrel contraceptive implant.

This paper reviews pharmacokinetic and pharmacodynamic studies with Implanon, which provides serum etonogestrel levels sufficient to inhibit ovulation within 8 h of insertion. After a peak of 813 pg/ml at 4 days, levels reach steady state (200 pg/ml) after 4-6 months and remain sufficient to prevent ovulation for 3 years. Variability is lower than with Norplant. Etonogestrel levels are similar in most ethnic groups, but 40% higher in women weighing < 50 kg. After implant removal, etonogestrel is not detectable within 1 week. Implanon inhibits ovulation by preventing the mid-cycle luteinizing hormone peak. Although it initially suppresses follicular development and estradiol production, ovarian activity slowly increases after 6 months, and follicle stimulating hormone and estradiol levels are almost normal. Endogenous progesterone levels remain in the subovulatory range for > 3 years in most subjects. In ovarian ultrasound studies, ovulation occurred in < 5% of users after 30 months of use. Ovulation was observed in most women within 3-4 weeks of implant removal. The pharmacokinetics and pharmacodynamics of Implanon indicate that it has high contraceptive efficacy, as reflected in a zero pregnancy rate over 5,629 woman-years of use. Its excellent reliability, ease of use, and reversibility make Implanon a valuable addition to current contraceptives.

Contraceptive Agents, Female↗
PubMed1999

Double-blind, placebo-controlled study of the effects of tibolone on bone mineral density in postmenopausal osteoporotic women with and without previous fractures.

A 2-year placebo-controlled, randomized, two-center prospective study was carried out to assess the effects of tibolone (Org OD14, Livial) on trabecular and cortical bone mass and bone biochemistry parameters in elderly postmenopausal women with and without previous fractures. In total, 107 subjects, 71 with fractures and 36 without fractures, were randomized to tibolone (n = 64) or placebo (n = 43). Their mean age was 63.1 years. Bone mineral density (BMD) (g/cm2) was assessed at baseline and every 6 months for 2 years by dual-energy X-ray absorptiometry (DXA). Mean baseline values were 0.79 and 0.80 for the lumbar spine in the tibolone and placebo groups, respectively, and for the femoral neck 0.64 in both groups. Serum and urinary bone biochemistry parameters were measured concurrently. An analysis of variance (ANOVA) model including center and group was applied. The completers' group was the primary subset for the analysis; the intention-to-treat (ITT) group was also analyzed. Results are expressed as the percentage change at 24 months and the annual rate of change percentage year. The tibolone group showed an overall mean increase (vs. placebo) in BMD at the lumbar spine of 7.2% (p < 0.001) and for the femoral neck 2.6% (p < 0.001). In subjects with previous fractures increases were 6.0% and 4.0% for the lumbar spine and femoral neck, while in those with no fractures, respective changes were 8.9% and 1.1%. Overall changes in the placebo group were 0.9% and -1.6% for the lumbar spine and femoral neck, respectively. A significant fall in bone biochemistry parameters showed that tibolone inhibits osteoclastic activity. In conclusion we have found that tibolone 2.5 mg induces significant increases of trabecular and cortical bone mass in elderly postmenopausal osteoporotic women with and without previous fractures.

Absorptiometry, Photon↗
PubMed1998

Safety, tolerability, and pharmacokinetics of a novel, selective antiprogestagen (Org 31710) in healthy male volunteers.

The safety and tolerability as well as pharmacokinetics of a new selective antiprogestagen, Org 31710, were studied after oral administration of single doses of 10, 25, 50, or 75 mg to 24 healthy male volunteers. Per dose-group, five subjects received active and one subject received placebo treatment. In subjects receiving 75 mg, the effects of Org 31710 on serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were also studied. No adverse or seriously adverse events were observed. All doses of Org 31710 were well tolerated. Characterization of the Org 31710 plasma pharmacokinetics revealed a statistically significant deviation from linearity: the dose normalized Cmax (nCmax) and dose normalized area under the curve (nAUC) values were significantly lower for the higher dosages (p < 0.05). Furthermore, tmax tended to decrease (from 1.6 to 0.9 h), whereas the elimination half-life (t1/2) tended to increase (from on average 45 to 57 h) with increasing dose. Org 31710 did not have any effect on serum levels of FSH, LH, and testosterone. In conclusion, Org 31710 appears to be a safe and well-tolerated compound in the dosage range studied.

Adolescent↗
PubMed1998

A 4-year pilot study on the efficacy and safety of Implanon, a single-rod hormonal contraceptive implant, in healthy women in Thailand.

OBJECTIVE: To investigate the contraceptive efficacy, safety and acceptability of a new single-rod, progestogen-only contraceptive implant (Implanon). METHODS: In an open, non-comparative pilot study, 100 healthy women received a contraceptive implant containing the progestogen etonogestrel (3-ketodesogestrel) for 2 years with an optional extension up to 4 years. RESULTS: Subjects were exposed to Implanon for 296.1 woman-years. There were no pregnancies during the study. Per 90-day reference period, the median number of bleeding-spotting days was 10 and the median number of bleeding-spotting episodes was 2. Amenorrhea occurred in 24-39% of subject during the first 2 years and in about 20% in those who continued in the 3rd and 4th years. The most common drug-related adverse event was headache (7%). A slight increase in body mass index was observed. Only a few subjects discontinued treatment early, due to bleeding irregularities (6%) or amenorrhea (1%). The cumulative discontinuation rates were 13.4% after 2 years, 25.3% after 3 years and 28.0% after 4 years of use. Within 3 months of implant removal, six normal pregnancies occurred, indicating a rapid return of fertility. The average time taken for insertion of the implant was 0.5 min, compared with 2.5 min for removal. CONCLUSIONS: Implanon demonstrated excellent contraceptive efficacy and was well tolerated during up to 4 years of use. The vaginal bleeding pattern was variable and was characterized by relatively few bleeding events, but proved acceptable to most subjects. Because of its single-rod design, Implanon was quickly inserted and removed without complications.

Adult↗
PubMed1997

A prospective, randomized study to assess the tolerance and efficacy of intramuscular and subcutaneous administration of recombinant follicle-stimulating hormone (Puregon).

OBJECTIVE: To compare local tolerance and clinical efficacy after i.m. or s.c. injection of recombinant FSH (Puregon; NV Organon, Oss, The Netherlands). DESIGN: An open-label, prospective, randomized, group-comparative, multicenter study. SETTING: Twelve IVF clinics in 10 countries. PATIENT(S): Two hundred eighteen infertile pituitary-suppressed women undergoing IVF-ET were randomized, of whom 195 (i.m., n = 77; s.c., n = 118) received recombinant FSH. INTERVENTION(S): One cycle of controlled ovarian hyperstimulation induced by either i.m. or s.c. injection of recombinant FSH, followed by IVF-ET. MAIN OUTCOME MEASURE(S): Local tolerance symptoms, number of oocytes retrieved, ongoing pregnancy rate. RESULT(S): The incidences after i.m. injection of bruising, pain, redness, swelling, and itching were 37.7%, 31.2%, 13.0%, 7.8%, and 6.5%; after s.c. injection, the corresponding figures were 54.2%, 28.0%, 16.1%, 5.9%, and 3.4%. Only bruising was significantly lower in the i.m. group, which could be attributed to the more visible superficial injection site with s.c. administration. The overall occurrence of local symptoms were 63.6% after i.m. injection and 68.6% after s.c. injection. The mean numbers of oocytes recovered were 9.8 (i.m) and 10.4 (s.c.) and the ongoing pregnancy rates per attempt were 27.1% (i.m.) and 26.1% (s.c.), respectively. CONCLUSION(S): There were no marked differences in local tolerance symptoms and clinical efficacy between i.m. and s.c. administration of recombinant FSH.

Adult↗
PubMed1997

Tibolone: influence on markers of cardiovascular disease.

Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties relieves climacteric symptoms and prevents postmenopausal bone loss. The influence of tibolone treatment on coagulation, fibrinolysis, and lipid metabolism was investigated in 91 healthy late postmenopausal women. They were randomly assigned in a double-blind, placebo-controlled 2-year study to receive either tibolone 1.25 mg (n = 36, 29 completed) or 2.5 mg (n = 35, 28 completed) or placebo (n = 20, 13 completed). The biochemical markers of lipid metabolism, fibrinolysis, and coagulation were measured every 3 months. In both tibolone groups a similar (approximately 30%) decrease in high density lipoprotein cholesterol and a corresponding lowering of apolipoprotein A-1 (P < 0.001) was detected. Also serum total cholesterol and triglycerides were reduced (approximately 15%; P < 0.01), whereas low density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) were unaffected by tibolone. The two dose levels of tibolone resulted in a similar, marked lowering (approximately 30%) of tissue plasminogen activator and plasminogen activator inhibitor activity as compared with placebo (P < 0.001). Plasminogen increased (approximately 15%; P < 0.001) in both groups. Fibrinogen was lowered (P < 0.01) in the low-dose group, and antithrombin III remained unchanged. The overall effect on hemostatic factors of the present doses of tibolone in healthy, late postmenopausal women tends towards increased fibrinolysis and unchanged coagulation. This may be beneficial and might theoretically counterbalance the potentially negative effect of the decrease in high density lipoprotein cholesterol.

Aged↗
PubMed1996

The effect of add-back treatment with tibolone (Livial) on patients treated with the gonadotropin-releasing hormone agonist triptorelin (Decapeptyl).

OBJECTIVE: To assess whether tibolone can prevent the bone loss and symptomatic side effects normally associated with GnRH agonist (GnRH-a) use and whether tibolone modifies the effect of GnRH-a on endometriosis. DESIGN: Prospective, double-blind, placebo-controlled, group comparative study. SETTING: Gynecological research unit in a London teaching hospital. PATIENTS: Twenty-nine patients with endometriosis and two with fibroids. INTERVENTIONS: Six months of treatment with 3.75 mg/mo IM triptorelin combined with daily tablets of either placebo or 2.5 mg tibolone. MAIN OUTCOME MEASURES: Daily symptom diary for hot flushes and bleeding episodes, laparoscopic scoring of endometriosis, endocrine and biochemical changes, and bone mineral density scans. RESULTS: Lumbar spine bone mineral density decreased significantly from baseline in the placebo group (-5.1%) but not in the tibolone group (-1.1%). The frequency of hot flushes and sweating episodes was reduced significantly by tibolone. There was no difference between the two treatment groups with regard to the endometriosis scores. CONCLUSIONS: The addition of tibolone to GnRH-a treatment reduces the bone loss and vasomotor symptoms that normally occur with GnRH-a, thus making long-term treatment with GnRH-a safer and more acceptable. It does not negate the therapeutic effect of GnRH-a on endometriosis.

Adult↗
PubMed1996

Effects of two doses of tibolone on trabecular and cortical bone loss in early postmenopausal women: a two-year randomized, placebo-controlled study.

The present randomized, double-blind, placebo-controlled, 2-year study is the first to evaluate the effect of 1.25 and 2.5 mg tibolone daily oral administration on trabecular and cortical bone loss in early postmenopausal women. Ninety-four healthy, normal weight, nonsmoking women participated 1-3 years following spontaneous menopause. Twenty-three subjects were randomized to the placebo group, 36 to the 1.25 mg/day tibolone group, and 35 to the 2.5 mg/day tibolone group. Bone density was assessed at 6 month intervals. Spinal trabecular bone density (BD) was measured with quantitative computed tomography. Phalangeal cortical BD was measured by radiographic absorptiometry. The 2-year change vs. baseline in the placebo group for trabecular BD was -6.4% (95% confidence interval -8.1 to -4.7). Cortical BD did not change significantly. At 24 months both tibolone groups showed a statistically significantly higher trabecular [9.4% (6.6-12.2) for the 1.25 mg group and 14.7% (11.8-17.5%) for the 2.5 mg group] and phalangeal BD [4.4% (1.5-7.4) for the 1.25 mg group and 6.8% (3.8-9.8) for the 2.5 mg group] as compared to the placebo group. After 2 years of tibolone in both regimes, trabecular and phalangeal BD was significantly higher as compared to pretreatment values. At 24 months the 2.5 mg group showed a significantly higher trabecular (p < 0.001) but not phalangeal (p = 0.064) BD compared to the 1.25 mg group. Tibolone prevents early postmenopausal bone loss by inducing an increase in trabecular and phalangeal BD.

Absorptiometry, Photon↗
PubMed1995

A prospective, randomized, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization.

Urinary follicle stimulating hormone (FSH) is being used for the treatment of human infertility. Recently, FSH manufactured by means of recombinant DNA technology with a much higher purity (> 99%) has become available. A prospective, randomized, assessor-blind, multicentre (n = 18) study was conducted in infertile women undergoing in-vitro fertilization comparing recombinant FSH (Org 32489, Puregon) and urinary FSH (Metrodin). Eligible subjects were randomized (recombinant versus urinary FSH = 3:2) and pretreated with buserelin for pituitary suppression. FSH was given until three or more follicles with a diameter of at least 17 mm were seen. After oocyte retrieval, fertilization routines were applied according to local procedures. No more than three embryos were replaced. In all, 585 subjects received recombinant FSH and 396 urinary FSH. Significantly more oocytes were retrieved after recombinant FSH treatment (mean adjusted for centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancy rates per attempt and transfer in the recombinant FSH group were 22.17 and 25.97% respectively, and in the urinary FSH group, 18.22 and 22.02% respectively (not significant). Ongoing pregnancy rates including pregnancies resulting from frozen-thawed embryo cycles were 25.7% for recombinant and 20.4% for urinary FSH (P = 0.05). Compared to urinary FSH, the total dose of FSH was significantly lower with recombinant FSH (2138 versus 2385 IU, P < 0.0001) in a significantly shorter treatment period (10.7 versus 11.3 days, P < 0.0001). No clinically relevant differences between recombinant and urinary FSH were seen with respect to safety variables. It is concluded that recombinant FSH (Puregon) is more effective than urinary FSH in inducing multifollicular development and achieving an ongoing pregnancy.

Cell Nucleus↗
PubMed1994

The effects of CTR-24, a biphasic oral contraceptive combination, compared to Diane-35 in women with acne.

One-hundred-and-eighty-three women were enrolled in an open, randomized, multicentre study in which the effects on acne of a low-dose biphasic oral contraceptive containing a daily dosage of 25 micrograms desogestrel and 40 micrograms ethinylestradiol (7 days) and a daily dosage of 125 micrograms desogestrel and 30 micrograms ethinylestradiol (15 days) were compared to Diane-35 containing a daily dosage of 2.0 mg cyproterone acetate and 30 micrograms ethinylestradiol (21 days) during four cycles of treatment. Clinical and photographic evaluation of acne plus laboratory assessments were done before treatment and at the end of cycle 4. A reduction with regard to the number of lesions and the degree of severity was observed in both groups. No differences were found between the two treatments in the clinical and photographic evaluation. In both treatment groups, a decrease in total testosterone and 3 alpha-17 beta-androstanediol glucuronide was observed and an increase in SHBG. The decrease in 3 alpha-17 beta-androstanediol was statistically significantly more pronounced in the Diane-35 group.

Acne Vulgaris↗
PubMed1994

Recombinant human follicle-stimulating hormone and ovarian response in gonadotrophin-deficient women.

Seven women suffering from hypogonadism due to previous hypophysectomy, isolated gonadotrophin deficiency, or Kallman's syndrome [median age 39 years (range 24-45)] volunteered to participate in a study to assess ovarian response following multiple-dose administration of recombinant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone (LH) concentrations were 0.25 (< 0.05-1.15) IU/l and 0.06 (< 0.05-0.37) IU/l, respectively. Subjects received daily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day, week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling and sonographic investigations were performed on alternate days. Steady-state FSH concentrations were reached approximately 3-5 days after alterations of the doses administered. Maximum FSH concentrations were between 7.1 and 11.8 IU/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (INH) (response failure possibly due to early ovarian failure or resistant ovary syndrome) in two subjects, analysis of ovarian response was restricted to five volunteers. Serum androstenedione levels showed no significant changes during rhFSH administration. Although serum immunoreactive INH concentrations reached normal late follicular values [659 (388-993) IU/l], serum oestradiol revealed only a minor increase [77 (18-210) pmol/l]. Moreover, growth of (multiple) ovarian follicles was observed up to pre-ovulatory sizes (> 15 mm) in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Intermittent bromocriptine treatment for the induction of ovulation in hyperprolactinemic patients.

Postovulatory treatment with bromocriptine bears a potential teratogenic risk. Therefore, after restoration of the menstrual cycle in 20 infertile hyperprolactinemic anovulatory patients, treatment was restricted to the follicular phase and the periovulatory period. The resulting intermittent treatment regimen using a dose of 5 mg of bromocriptine/day yielded ovulatory cycles in all 20 patients. Fifteen pregnancies were achieved in thirteen patients, two women becoming pregnant twice. Discontinuation of treatment after ovulation caused hyperprolactinemia during the luteal phase. This did not seem to interfere with the establishment and maintenance of pregnancy. Hyperprolactinemia during the follicular phase may be related to luteal insufficiency.

Adult↗