Induction of ovulation with low-dose estrogen-progestin therapy in amenorrheic patients

Sixteen amenorrheic patients, five with ovarian and 11 with hypothalamic failure, were treated for three cycles with a biphasic low-dose estrogen-progestin regimen consisting for esterified estrogen, 1.5 mg/day for 21 days, combined for the last 7 days with norethisterone acetate, 5 mg/day. Serum FSH and LH decreased significantly (P less than 0.01) during treatment in the ovarian failure group, and FSH in the hypothalamic failure group. Estradiol levels increased on average two-fold during treatment and decreased again after treatment, these changes being slower in the hypothalamic than in the ovarian failure group. Withdrawal bleeding occurred in all patients during the treatment cycles. After treatment, six patients with hypothalamic failure had spontaneous menstrual bleedings. Judged by serum progesterone measurements, one ovulation occurred in each group during the treatment cycles, and in the hypothalamic failure group, two ovulations were observed 3 wk after treatment. Four women with secondary amenorrhea are presented, in whom conception occurred during biphasic estrogen-progestin treatment; three of these cases had hypergonadotrophic ovarian failure. Our results suggest that low-dose estrogen-progestin treatment may induce ovulation in selected cases of hypothalamic and also of ovarian failure.     

Cyclical dydrogesterone in secondary amenorrhea: results of a double-blind, placebo-controlled, randomized study.

Secondary amenorrhea in women with normal estrogen levels increases the risk of endometrial carcinoma. Cyclical dydrogesterone induces regular withdrawal bleeding and effectively protects the endometrium of postmenopausal women receiving estrogens. In order to assess the efficacy of dydrogesterone in inducing regular withdrawal bleeds in premenopausal women with secondary amenorrhea or oligomenorrhea and normal estrogen levels, a double-blind, randomized, placebo-controlled, multicenter study was conducted in 104 women using cyclical dydrogesterone as is used for estrogen replacement therapy. Treatment consisted of dydrogesterone (10 mg/day on days 1-14 followed by placebo on days 15-28 of each cycle) given for six cycles of 28 days. The control group received placebo throughout the six cycles. Bleeding was documented by the patient on diary cards. The number of women with withdrawal bleeding during the first cycle was twice as high in the dydrogesterone group as in the placebo group (65.4% vs. 30.8%; p = 0.0004). Superiority of dydrogesterone was also observed for regularity of bleeding over the six cycles (p < 0.0001), although endometrial thickness after six cycles did not differ between the groups. In conclusion, dydrogesterone is significantly superior to placebo in inducing withdrawal bleeding, and maintaining regular bleeding, in women with secondary amenorrhea and normal estrogen levels.     

Induction of ovulation with pulsatile LHRH in anovulatory women

Nine anovulatory patients were treated by administering pulsatile LHRH (2-20 micrograms, i.v. at 90 min intervals) for 15-58 days. These patients consisted of 4 women with hypothalamic amenorrhea, one women with oligomenorrhea, 2 women with polycystic ovarian disease (PCOD) and 2 women with hyperprolactinemic amenorrhea. Four of them were involuntarily infertile. The pulsatile LHRH therapy induced follicular maturation and ovulation, as evidenced by increased plasma estradiol levels followed by a midcycle LH surge and subsequent rise in plasma progesterone (P) levels, in 8 of the 9 patients. One patient with PCOD failed to ovulate. All of 11 treatment cycles were ovulatory in the 8 patients. A maximal P level of below 10 ng/ml was seen in 3 of the 11 induced ovulatory cycles, indicating corpus luteum insufficiency. Luteolysis occurred soon after discontinuing the pulsatile LHRH administration at the mid to late luteal phase in 3 ovulatory cycles. One of the 4 infertile women became pregnant. The results indicate that chronic pulsatile administration of LHRH is useful in inducing ovulation not only in hypothalamic amenorrhea, but also in PCOD and hyperprolactinemic amenorrhea. They also suggest that although a possible augmentation of the hypothalamic LHRH release at the preovulatory phase cannot be denied, a series of endocrine events during the human menstrual cycle may be regulated by the feedback action of the ovarian signals on the pituitary under a fixed input of the hypothalamic LHRH.     

Attempts to induce ovulation in amenorrheic patients using D-Ala-6-LH-RH propylamide.

Thirteen amenorrheic patients, two with primary amenorrhea, and eleven with secondary amenorrhea, including five with anorexia nervosa, were treated with an analog of LH-RH, D-Ala-6-desGly-10-LH-RH propylamide (D-Ala-6-LH-RH PA). The patients were follwed with checks of daily basal body temperature, cervical mucus characteristics, urinary total estrogens and pregnanediol, plasma LH and FSH, and twice-weekly clinical checkups. D-Ala-6-LH-RH PA was given continuously for 11 days at a dose of 50 microgram im from the 4th day of a steroid-induced cycle. Ethynyl estradiol (50 microgram orally) was given twice on day 14 followed by 250 microgram of D-Ala-6-LH-RH PA for the following 3 days. All the treated cycles were monophasic. Withdrawal bleeding occured in nine patients from the 4th to 6th days posttreatment. A significant total maximal increment in estrogens was found in seven patients, which was higher than the values obtained previously in the same patients with human menopausal gonadotropin. One patient conceived in the cycle immediately following discontinuation of treatment, indicating a possible effect of analog on the follicular development during the treatment; a normal baby was delivered. A second patient conceived three cycles afterwards, and two other patients began normal menstrual cycles.     

Time of initiation of clomiphene citrate and pregnancy rate in polycystic ovarian syndrome.

OBJECTIVE: To investigate whether the timing of clomiphene citrate (CC) administration affects hormonal levels, follicular growth, endometrial thickness, and ovulation and pregnancy rates in women with polycystic ovarian syndrome (PCOS). METHODS: Of the 78 infertile women with PCOS who participated in this prospective, double-blind, randomized clinical trial, 37 collectively underwent 71 cycles of CC (100 mg/day) on days 1 through 5 of the menstrual cycle (group 1) and 41 collectively underwent 73 cycles of CC at the same concentration on days 5 through 9 (group 2). Hormonal levels, follicular growth, endometrial thickness, and ovulation and pregnancy rates were compared. RESULTS: The mean number of follicles and the maximum follicular size were greater in group 2. However, ovulation rates were 72.8% in group 1 and 70.8% in group 2 (P=.78), and pregnancy rates were 40.5% in group 1 and 19.5% in group 2 (P=.04). CONCLUSION: Treatment with CC is associated with higher rates of pregnancy if started early (days 1-5) in the menstrual cycle.     

Effects of initiation day of clomiphene citrate on the endometrium of women with regular menstrual cycles

OBJECTIVE: To investigate the effects of initiation time of clomiphene citrate (CC) on the endometrium of women with regular menstrual cycles. DESIGN: Randomized, double-blind, cross-over study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. PATIENT(S): Thirty-three healthy female volunteers with regular menstrual cycles. INTERVENTION(S): The volunteers were randomized to receive either 100 mg of CC on days 1-5 and placebo on days 5-9 (study group) or placebo on days 1-5 and CC on days 5-9 (control group). After a wash-out period of 1 month of CC treatment, the medication was switched in each group. Ultrasonography was performed daily after day 10 of the cycle to detect ovulation. Ultrasonography for endometrial appearance and thickness, endometrial sampling, and blood samples obtained for determination of E(2) and P levels were performed 7 days after ovulation in both groups. MAIN OUTCOME MEASURE(S): Morphometric analysis, histologic dating, and ultrasonographic appearance and thickness of the endometrium. RESULT(S): Morphometric parameters, histologic dating, and ultrasonographic appearance and thickness of the endometrium were similar in both groups. CONCLUSION(S): Starting CC on either day 1 or day 5 of the menstrual cycle did not have any differential effects on the endometrium of women with regular menstrual cycles, particularly regarding the morphometric analysis, histologic dating, or ultrasonographic appearance.     

Endocrinology of gonadotropin-releasing hormone induced cycles in hypothalamic amenorrhea: the role of the pulse dose.

OBJECTIVE: To find the treatment regimen giving a maximum chance of ovulation and a minimal chance of multiple follicular development in pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with hypothalamic amenorrhea. DESIGN: We propectively studied the endocrinology of cycles induced with 5, 10, and 20 micrograms GnRH pulse doses, randomly assigned per patient, comparing this with the endocrinology of spontaneous menstrual cycles. SETTING: All patients were treated at the Academic Hospital of the Vrije Universiteit, Division of Reproductive Endocrinology and Fertility. PATIENTS: Fifteen patients with hypothalamic amenorrhea were treated for one to three cycles; 14 normally cycling volunteers were studied for one cycle. MAIN OUTCOME MEASURE: Number of ovulations per pulse dose; luteinizing hormone, follicle-stimulating hormone, total urinary estrogens (Es), and pregnanediol were measured per cycle day and per stimulation day. RESULTS: The endocrinology of all ovulatory cycles remained within the normal range. First treatment cycles showed significantly higher ovulation rates compared with subsequent cycles. Significantly more anovulation was observed in cycles with 5-micrograms pulse doses. Luteal Es were significantly higher in induction cycles compared with controls. CONCLUSIONS: The optimum treatment regimen should be to start induction with 5 micrograms/pulse in the first cycle and to raise the dose to 10 micrograms/pulse in subsequent cycles, regardless of the outcome of the first cycle. After ovulation, the pulse interval should be changed to 240 minutes.     

Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea

OBJECTIVE: To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. SETTING: Gynecological Endocrinology Research Center, University of Siena (Italy). PATIENTS: 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. DESIGN: Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. MAIN OUTCOME MEASURES: Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Results: Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. CONCLUSIONS: Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.     

Evaluation of d-norgestrel 1.0 mg in cyclic regimen

111 women took a total of 584 cycles of 1.0 mg norgestrel for 21 days out of a 28 day cycle, in a trial of a low-dose progestin-only oral contraceptive, intended to avoid the side effects of estrogen and the menstrual irregularity of mini-pills. This study followed an 18 month blind trial of norgestrel, .5, 1.0 and 1.5 mg in 100 patients, which found the 1.0 mg dose most suitable. 33.6% of these subjects had used pills within the last 90 days, and all were private patients of the Western Gynecological and Obstetrical Clinic, Inc. 97.7% of menstrual cycles before, and 81% during the trial were 21-35 days in length; the mean cycle length was 28.8 days before, and 29.0 days during treatment. Menses lasted a mean of 4.8 days before and 5.6 days during norgestrel. Menstrual flow became lighter in most, but breakthrough bleeding increased from 1.8% to 10%, spotting from 6.3% to 30.7%, and amenorrhea from 4.5% to 11.1%. Dropouts included 10 for bleeding, 5 for weight gain, 3 for acne, and 1 each for edema, generalized somatic complaints, irritability, depression and decreased libido. One pregnancy resulted from patient failure. The authors concluded that, except for the "fastidious," most women should not object to this degree of irregular bleeding, once it becomes "individualized."     

黄体早期服用低剂量米非司酮作为妇女常规避孕方法的初步研究

目的:探讨米非司酮用于妇女常规避孕的可行方法。方法:共74例自愿受试人员,于规律月经第15日开始,口服米非司酮5 mg,按疗程递减顺序分别为A组(研究Ⅰ期)每日1次连服4天,B组(研究Ⅱ期)每日1次连服3天,C组(研究Ⅲ期)隔日1次共服2天,观察避孕效果及月经周期改变情况,对可能月经推迟3天及以上者行尿HCG、B超等检查排除早孕。结果:A组43例受试125周期,122例次月经如期来临,3例次月经推迟6~9天,尿HCG、B超等检查阴性,有效率100.0%,月经正常率97.6%。B组68例(A组43例+新入受试25例)受试286周期,282例次月经如期来临,4例次月经推迟5~8天,尿HCG、B超等检查阴性,有效率100.0%,月经正常率98.6%。C组6例(新入受试人员)受试12周期,9例次月经推迟6~9天,尿HCG、B超等检查阴性,有效率100.0%,月经正常率25.0%。A、B两组共获411受试周期,避孕有效率均达100.0%,月经正常率98.3%;C组月经周期正常率显著低于A、B组(P0.01),研究暂时终止。A、B两组避孕效果及对月经的影响差异无统计学意义(P0.05)。结论:黄体早期(内膜分泌期早期)阶段短程、小剂量应用米非司酮有较好的避孕效果,且对月经周期无明显的影响,月经规律者可用于每月的常规性避孕。初步研究认为较佳的剂量-时效关系为米非司酮5mg/d连用3天。     

The treatment of luteal phase defects with pulsatile infusion of gonadotropin-releasing hormone

Because pulsatile administration of gonadotropin-releasing hormone (GnRH) can initiate normal follicular maturation and corpus luteum function in women with hypothalamic amenorrhea, the authors attempted to treat five women with inadequate and one with short luteal phase with GnRH therapy. Pulsatile administration of GnRH (5 micrograms intravenously every 90 minutes) was begun on days 1 to 4 and continued throughout the cycle. Blood levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, and progesterone were monitored daily throughout the control and treatment cycles. There were 12 GnRH treatment cycles, all of them ovulatory. The length of the induced luteal phases varied from 11 to 17 days in all patients. Mean progesterone levels during GnRH treatment were significantly increased over those of the matched control cycles (control cycle 3.5 +/- 0.5 ng/ml; treatment cycle 8.2 +/- 1.45 ng/ml [mean +/- standard error]). Endometrial biopsies obtained during the luteal phase (days 25 to 27) in five women were in phase during the GnRH treatment cycle, in contrast to the control cycle in which they were two or more days out of phase. One patient achieved pregnancy during the treatment cycle, but aborted spontaneously at 8 1/2 weeks. The data demonstrate that pulsatile GnRH infusion, when initiated in the early follicular phase, can restore normal corpus luteum function in women with luteal phase defects.     

A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.

OBJECTIVE: To establish whether initial screening characteristics of normogonadotropic anovulatory infertile women can aid in predicting live birth after induction of ovulation with clomiphene citrate (CC). DESIGN: Prospective longitudinal single-center study. SETTING: Specialist academic fertility unit. PATIENT(S): Two hundred fifty-nine couples with a history of infertility, oligoamenorrhea, and normal follicle-stimulating hormone (FSH) concentrations who have not been previously treated with any ovulation-induction medication. INTERVENTION(S): 50, 100, or 150 mg of oral CC per day, for 5 subsequent days per cycle. MAIN OUTCOME MEASURE(S): Conception leading to live birth after CC administration. RESULT(S): After receiving CC, 98 (38%) women conceived, leading to live birth. The cumulative live birth rate within 12 months was 42% for the total study population and 56% for the ovulatory women who had received CC. Factors predicting the chances for live birth included free androgen index (testosterone/sex hormone-binding globulin ratio), body mass index, cycle history (oligomenorrhea versus amenorrhea), and the woman's age. CONCLUSION(S): It is possible to predict the individual chances of live birth after CC administration using two distinct prediction models combined in a nomogram. Applying this nomogram in the clinic may be a step forward in optimizing the decision-making process in the treatment of normogonadotropic anovulatory infertility. Alternative first line of treatment options could be considered for some women who have limited chances for success.     

Dopamine antagonists in anovulation?

Increased hypothalamic dopamine turnover may prevent the ovulatory LH peak by different mechanisms and may in this way result in anovulation. Ten patients with anovulatory menstrual cycles who had been treated with clomiphene citrate without success were given the dopaminolytic drug pimozide (Antalon) at a dose of 5 mg/day orally either from day 7 to day 11 (7 women; group 1) or from day 11 to day 15 of the menstrual cycle (4 women; group 2). One patient from group 2 ovulated during the treatment cycle. A further woman from this group exhibited an LH peak, but did not ovulate, whereas a slow increase of the circulating LH level was recorded in the remaining two patients. Systematic investigations should clarify whether introduction of dopaminolytic therapy in the treatment of hypothalamic anovulation may be justified.     

Effect of short-term cyclic administration of cyproterone acetate on pituitary-ovarian function in the human

Short courses of cyproterone acetate, a compound with progestational and antiandrogenic activities, were administered to normally menstruating women during different phases of the menstrual cycle to suppress growth and maturation of the follicles and corpus luteum function. Postovulatory administration of 20 mg of the drug daily for 8 days to two women delayed menstruation by 4 to 6 days, followed by prolonged bleeding and short post-treatment cycles. Plasma levels of progesterone were suppressed temporarily during therapy, but increased immediately after cessation of treatment. Administration of 10 mg of the drug for 8 days during the early follicular phase to two women resulted in irregular bleeding, short cycles, and decreased plasma levels of progesterone throughout the cycle. Reduction of the dose to 2.5 mg during the early follicular phase in two other women also resulted in irregular cycles. When the 2.5-mg dose was administered to three women from the 8th to the 15th days of the cycle, vaginal bleeding and cycle length were normal. Plasma levels of luteinizing hormone and progesterone were suppressed during therapy. In one subject, cervical mucus was found to be hostile to sperm penetration in all three treatment cycles. The results indicate that, with cyclic administration of low doses of cyproterone acetate to women during the late follicular phase, it may be possible to interrupt pituitary-ovarian function, as well as sperm transport through the cervical mucus.     

Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective,double-blind,placebo-controlled trial

OBJECTIVE: To evaluate the effects of short-course administration of dexamethasone (DEX) combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal DHEAS levels. DESIGN: Prospective, double-blind, placebo-controlled, randomized study. SETTING: Referral university hospitals. PATIENT(S): Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC. INTERVENTION(S): The treatment group received 200 mg of CC from day 5 to day 9 and 2 mg of DEX from day 5 to day 14 of the menstrual cycle. The control group received the same protocol of CC combined with placebo. MAIN OUTCOME MEASURE(S): Follicular development, hormonal status, ovulation rate, pregnancy rate. RESULT(S): Mean follicular diameters were 18.4124 +/- 2.4314 mm and 13.8585 +/- 2.0722 mm for the treatment and control groups, respectively. Eighty-eight percent of the treatment group and 20% of the control group had evidence of ovulation. The difference in the cumulative pregnancy rate in the treatment and control groups was statistically significant. CONCLUSION(S): Hormonal levels, follicular development, and cumulative pregnancy rates improved with the addition of DEX to CC in CC-resistant patients with PCOS and normal DHEAS. This regimen is recommended before any gonadotropin therapy or surgical intervention.     

国产三相避孕片对月经失调妇女血脂的影响

研究三相避孕片治疗功血及闭经等疾病对血脂的影响.患者按21随机分配为试验组60例和对照组32例.试验组用三相片3周期,对照组EE0.03mg/日,连服20天,自服EE第11天起序贯加用MPA4mgBid,连服10天,共用3周期.两组用药前及停药后测量血脂.结果功血患者血脂变化TC及LDL-C上升具有统计学意义,但均在正常范围内波动.元排卵型功血的血脂影响最小;CT/HDL-C及LDL-C/HDL-C变化均无统计学意义.对闭经妇女,TC/HDL-C,LL-C/HDL-C均上升,有显著性差异,亦在正常范围波动.提示三相避孕片作为治疗功血控制月经周期,对闭经作人工周期治疗等,对血脂代谢影是安全的,其血脂代谢血变化也是在正常范围内波动.     

The effect of progesterone in adolescent girls and young women with functional uterine bleeding

The detailed menstrual records of 24 adolescent girls and young women with functional uterine bleeding are given. These subjects were given progesterone or anhydrohydroxy progesterone, and the effect on the menstrual pattern was observed over a period of many months in most cases. In general, the administration of approximately 30 mg. of progesterone was followed by cessation of bleeding within ten days of the last injection. Progesterone deprivation bleeding occurred frequently, thereby explaining the bleeding occurring in the first few days after therapy. In about one-third of the observations, normal cycles occurred for four months or more after therapy, whereas in another third there was a recurrence in less than four months. Even in these, however, there was no recurrence in the first month. In the final third of the observations, amenorrhea followed immediately or after two or three cycles.     

Changes in bone density in hemodialysed women treated with transdermal hormone replacement therapy

OBJECTIVES: Renal insufficiency in women can cause menstrual disturbances and changes of hormonal profile leading to the decrease of bone mass density. Drug administration during dialysis also influences the bone density and increases the risk of osteoporosis. The aim of the study is to assess the effect of transdermal hormonal replacement therapy (HRT) in hemodialysed patients with secondary amenorrhea on bone density. MATERIAL AND METHODS: 10 women aged from 22 to 45 years old were enrolled in the study. They received 17 beta-estradiol and norethisterone acetate in patches during 12 cycles. Densitometer of lumbar spine and serum estradiol concentration were measured before and after 12 cycles of therapy. RESULTS: The recurrence of regular vaginal bleeding, the increase of estradiol levels and bone mass density rate about 6% were observed. CONCLUSIONS: Transdermal hormonal replacement therapy in hemodialysed women with secondary amenorrhea revealed the efficacy of the treatment and prevention from osteoporosis.     

Induction of ovulation with clomiphene citrate in combination with metoclopramide in patients with amenorrhea of hypothalamic origin.

Literature data have demonstrated that the chronic use of metoclopramide (MCP), a dopamine antagonist, causes increased gonadotropin secretion in patients with hypothalamic amenorrhea but without triggering ovulation. It has also been observed that women with hypothalamic amenorrhea respond poorly to ovulation induction with clomiphene citrate (CC). On this basis, the objective of the present study was to determine the effect of MCP on the response to CC in patients with hypothalamic amenorrhea in order to evaluate the validity of the simultaneous use of these drugs as ovulation inducers in this type of chronic anovulation. Twenty-two patients with amenorrhea of hypothalamic origin were submitted to a randomized double blind study in which one tablet of 5 mg MCP or placebo was administered every 8 hours for 2 months. After the 30th day of medication (MCP or placebo), CC, 100 mg orally, was additionally administered to both groups for 5 days. Blood samples were collected on days 1, 15 and 30 during the first month of the study and on days 7, 14 and 21 after the last CC tablet during the second month, for later measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol and progesterone by radioimmunoassay. The group that received MCP showed a significant increase in LH and FSH during the first month of the study, as well as a slighter increase in estradiol. Prolactin increased only during the second stage of treatment. No significant increases in gonadotropins, prolactin or estradiol occurred in the placebo group. In the group treated with MCP, 40% of the patients ovulated after CC, with menstruation occurring in 60% of them. In the placebo group, 33.3% of the women ovulated after CC and 44.4% menstruated at the end of the study. We conclude that MCP increases the circulating levels of LH, FSH, estradiol and prolactin in patients with hypothalamic amenorrhea and low estrogen levels, supporting the hypothesis that an increase in hypothalamic dopaminergic tonus occurs in these patients. On the other hand, the combination of MCP and CC does not improve the rate of ovulation compared to placebo.     

Depressed prolactin levels in diabetic women with anovulation

The circulating levels of prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol-17 beta were determined by radioimmunoassay in 76 normal healthy women in the follicular phase of the menstrual cycle, 54 consecutive anovulatory non-diabetic women and 20 consecutive diabetic women with anovulation. An elevated plasma PRL concentration was found in 1/20 (5%) of the diabetic women and in 17/54 (32%) of the non-diabetic anovulatory women (p less than 0.05). Plasma concentrations of estradiol-17 beta and gonadotropins in diabetics did not differ (p greater than 0.05) from those found in non-diabetic women with anovulation. Diabetic women with secondary amenorrhea had significantly (p less than 0.05) lower plasma concentrations of PRL and estradiol-17 beta than non-diabetic women with amenorrhea and normal controls. Furthermore, this group of diabetic women had lower median plasma LH concentrations than the non-diabetics with secondary amenorrhea and normal controls, but this difference was not significant (p greater than 0.05). These data indicate that diabetic patients with anovulation have hypothalamic and/or pituitary defects. Furthermore, the low prolactin and LH levels despite a low estradiol-17 beta concentration may suggest an increased hypothalamic dopamine activity in patients with diabetes mellitus and secondary amenorrhea.