The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women.

Controversial effects of weight reduction on gonadotropin secretion in obesity have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring LH and FSH concentrations. We studied follicular phase nocturnal urinary (nu) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsulinemic clamp) during 1 menstrual cycle/30-day period before and after weight reduction in 10 severely overweight infertility patients (age, 29 +/- 3.1 yr; body mass index, 37.1 +/- 3.3 kg/m2; +/-SEM). A 6-week very low calorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH surge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6.06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), which was accounted for by a significant increase in nonoxidative glucose disposal (P = 0.003). Serum sex hormone-binding globulin concentrations increased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin concentrations decreased by 38%, those of leptin by 37%, those of androstenedione by 32%, those of testosterone by 20% (all P < 0.01), and those of dehydroepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH correlated negatively with glucose uptake (r = -0.76; P < 0.01) and the increase in serum sex hormone-binding globulin (r = -0.85; P < 0.005) and positively with the percent change in waist to hip ratio (r = 0.79; P < 0.01). The absolute nu-LH levels after weight reduction correlated significantly with fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were found between absolute levels or changes in nu-LH concentrations and leptin, IGF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH concentrations, a reduction in the LH/FSH ratio, and FSH predominance favoring folliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is possible that the decrease in LH secretion with weight reduction is more dependent on the absolute levels of insulin sensitivity than on the degree of general adiposity.

Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response.

The satiety factor leptin is expressed in several reproductive tissues, but its role in the control of reproductive physiology is not well understood. We studied leptin concentrations in the sera and follicle fluids of 52 women [body fat mass percentage (BFM%) range, 19.6-38.8%] undergoing pituitary down-regulation and ovarian hyperstimulation for in vitro fertilization (IVF) treatment. Fasting serum samples were collected 1) at maximal suppression before the initiation of gonadotropin treatment, 2) at maximal ovarian hyperstimulation, 3) at the time of oocyte retrieval, and 4) 16 days later when all subjects were under exogenous luteal support using 600 mg progesterone daily. Follicular fluid (FF) was obtained at oocyte retrieval from two representative preovulatory follicles in both ovaries. During ovarian hyperstimulation there was a significant 60% increase in serum leptin concentrations from 10.9 +/- 1.1 (SEM) to 15.7 +/- 1.5 ng/mL (P < 0.01) between suppression and maximal hyperstimulation, demonstrating that the ovarian functional state can affect serum leptin concentrations. A serum leptin increase of 22-198% during ovarian hyperstimulation was evident in 43 subjects, whereas in 9, leptin concentrations remained unchanged. A positive correlation between leptin change and BFM% (r = 0.55; P < 0.0005) was observed in the 43 leptin responders. The follicular fluid leptin level was similar to that in serum. In separate linear regression analysis, BFM% contributed to 59-64%, body mass index to 46-56%, and weight to 46-55% (all P < 0.001) of the variability in leptin concentrations at the 4 time points. The 20-fold increase in serum estradiol concentrations during IVF was not significantly correlated with changes in leptin concentrations. On the contrary, the relative serum leptin increase was negatively associated with the ovarian response to hyperstimulation, as revealed by the numbers of follicles (b = -0.28; r2 = 8.1%; P < 0.05) and oocytes retrieved (b = -0.39; r2 = 15.2%; P < 0.01). This relationship was further reflected in a positive correlation between the percent increases in leptin and FSH concentrations (r = 0.39; P < 0.01). The significant relationship of high leptin and reduced ovarian response was also maintained when the cumulative dose of FSH was used as a covariable. Reduced ovarian response was not a function of body mass index, BFM%, basal leptin levels, or insulin concentrations. Fasting serum insulin concentrations remained unchanged in response to IVF, but were positively correlated to serum leptin concentrations at all four time points. Our data suggest that leptin production may be influenced by the ovarian functional state. During IVF a high relative leptin increase is associated with adiposity and a reduced ovarian response. These observations support the possibility that high leptin concentrations might reduce ovarian responsiveness to gonadotropins. Hence, leptin might explain in part why obese individuals require higher amounts of gonadotropins than lean subjects to achieve ovarian hyperstimulation.

Conservative treatment of ectopic pregnancy.

As a conservative nonsurgical treatment of an early ectopic pregnancy, local prostaglandin, parenteral or local methotrexate, local hyperosmolar glucose, and also expectant management have been used successfully in selected cases. The success rate of conservative treatment has been 71%-100% and that of tubal patency after different kinds of conservative treatment 72-93% of patients. In the present study of expectant management in early ectopic pregnancy in patients with decreasing serum hCG levels, spontaneous resolution was observed in 64.6% of patients and in the total series of 207 ectopic pregnancies in 15.0% of patients. Expectant management of early ectopic pregnancy is recommended when emergency surgery is not needed on admission and the serum hCG level is decreasing as noted in two consecutive estimations with an interval of 1-2 days.

Urinary 6-keto-prostaglandin F1 alpha during ovulation induction.

To elucidate the role of the vasodilatory prostacyclin (PGI2) in human ovulation, urinary samples were collected from spontaneously ovulating women (n = 8) and from those undergoing ovulation induction with clomiphene (seven women, 9 cycles) and human gonadotropins (five women, 11 cycles). The samples were assayed for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a breakdown product of PGI2, employing high-pressure liquid chromatography and radioimmunoassay. The urinary 6-keto-PGF1 alpha was not consistently related to the menstrual cycle day at collection, the occurrence of spontaneous (n = 8) or induced (n = 11) ovulation, or the simultaneous concentration of estradiol in plasma. However, its concentrations both before and after the approximated time of ovulation during clomiphene (41.6 +/- 6.7 and 52.7 +/- 7.9 pmol/mmol creatinine, before/after, mean +/- standard error) or gonadotropin treatment (49.0 +/- 5.8 and 48.1 +/- 6.8 pmol/mmol creatinine) were higher (P less than 0.01) than those in spontaneously ovulating women (26.4 +/- 3.8 and 20.5 +/- 3.0 pmol/mmol creatinine, respectively). Multiple ovarian follicles, as assessed ultrasonographically, developed during four courses of the treatments with gonadotropins, and in three of them the urinary 6-keto-PGF1 alpha was high. The data suggest that treatment with clomiphene and gonadotropin is accompanied by increased production of PGI2, perhaps in the ovaries and/or in the kidneys. This may perhaps play a role in the etiopathogenesis of ovarian hyperstimulation syndrome.

Endocrinologic features of oligomenorrheic adolescent girls.

The plasma concentrations of sex hormones were measured in 45 oligomenorrheic and 28 regularly menstruating adolescent girls. Testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin levels were determined in blood samples collected during one menstrual cycle. The oligomenorrheic girls had significantly higher concentrations of luteinizing hormone, androstenedione, dehydroepiandrosterone-sulfate, and free testosterone than regularly menstruating girls. Sex hormone-binding globulin concentrations were significantly lower in the oligomenorrheic group. The oligomenorrheic girls were not obese. Signs of acne or hirsutism were absent or mild. Sixty-six percent of the oligomenorrheic cycles were ovulatory. The significance of the hormonal findings is discussed.

Sex hormone profiles in oligomenorrheic adolescent girls and the effect of oral contraceptives.

The hormonal profiles and the effect of oral contraceptives (OCs) on 16 oligomenorrheic and 10 regularly menstruating adolescent girls were studied. Testosterone, androstenedione, dehydroepiandrosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex-hormone-binding globulin were determined on blood samples obtained during a control cycle, during OC treatment, and during the follow-up cycle after discontinuation of OC use. The oligomenorrheic girls had significantly higher concentrations of androstenedione and total and free testosterone than regularly menstruating girls during the control cycle. Sex-hormone-binding globulin concentrations were significantly lower in the oligomenorrheic group. Both in oligomenorrheic and regularly menstruating girls OC treatment caused a decrease in the mean concentrations of all hormones, except prolactin, to similar levels. For 2 to 4 weeks after treatment the oligomenorrheic girls had significantly lower levels of androstenedione, total and free testosterone, and luteinizing hormone than before treatment. In the control group there were no significant differences between pretreatment and posttreatment hormone concentrations. The risks and benefits of prescribing OCs for oligomenorrheic adolescent girls are discussed.

PIP: The hormonal profiles and effect of oral contraceptives (OCs) on 16 oligomenorrheic and 10 regularly menstruating adolescent girls were studies. Testosterone, androstenedione, dehydroepiandrosterone, estradiol, progesterone, luteinizing hormone, follicle stimulating hormone, prolactin, and sex hormone binding globulin were determined on blood samples obtained during a control cycle, during OC treatment, and during the follow-up cycle after OC discontinuation. The oligomenorrheic girls had significantly higher concentrations of androstenedione and total and free testosterone than regularly menstruating girls during the control cycle. Sex hormone binding globulin concentrations were significantly lower in the oligomenorrheic group. Both inoligomenorrheic and regularly menstruating girls, OC treatment caused a decrease in the mean concentrations of all hormones, except prolactin, to similar levels. For 2-4 weeks after treatment, the oligomenorrheic girls had significantly lower levels of androstenedion, total and free testosterone, and luteinizing hormone than before treatment. In the control group, there were no significant differences between pretreatment and posttreatment hormone concentrations. The risks and benefits of prescribing OCs for oligomenorrheic adolescent girls are discussed.

Pulsatility of serum-luteinizing hormone during hyperstimulation with clomiphene citrate and human menopausal gonadotropin for in vitro fertilization.

The pulsatile pattern of gonadotropin secretion regulates follicular growth and corpus luteum function in normal cycles, but the role of endogenous gonadotropin pulses in hyperstimulated cycles is unclear. We studied pulsatility of serum-luteinizing hormone (LH) in the late follicular and midluteal phases in four women after hyperstimulation with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin, and in five women with normal untreated cycles. In the late follicular phase, the number, interval, amplitude, and area of LH pulses did not show significant differences between hyperstimulated and control cycles. In the midluteal phase, the long-lasting (greater than 90 minutes) LH pulses typical for the normal luteal phase, were not found after hyperstimulation. As the length of the luteal phase in these cases was normal, the significance of this finding remained obscure.

The influence of sperm morphology and the number of motile sperm inseminated on the outcome of intrauterine insemination combined with mild ovarian stimulation.

OBJECTIVE: To determine the influence of sperm morphology and the number of motile sperm inseminated on the outcome of IUI in hMG-stimulated cycles and to establish lower limits for these variables below which the expectation of pregnancy is limited. DESIGN: Retrospective study of data from 1990 to 1992. SETTING: Tertiary referral Reproductive Medicine Unit. PATIENTS: Couples with bilaterally patent fallopian tubes, and > or = 200,000 motile sperm recovered in a trial preparation before treatment. No other semen criteria were used to exclude couples. Women were stimulated with hMG irrespective of whether they were ovulatory or anovulatory. The study comprised 163 couples who underwent 330 cycles. MAIN OUTCOME MEASURES: Pregnancy rate (PR) per cycle was related to the percentage normal sperm morphology in the fresh semen sample and the number of motile sperm inseminated after sperm preparation by swim-up or Percoll gradients. RESULTS: The overall PR was 16.1% per cycle. The PR was highest in the first cycle of treatment (21.4%) and declined in the second and third cycles. The miscarriage rate was 10.4% and the incidence of multiple pregnancies was 13.9%. Two groups of patients were defined on the basis of sperm morphology: a "poor outcome" group ( < or = 10% normal) and a "good outcome" group ( > 10% normal). The PRs in these two groups were 4.3% and 18.2%, respectively, and the cumulative PRs after three cycles were 8.3% and 40.1%, respectively. The number of motile sperm inseminated did not significantly affect the PR. CONCLUSIONS: The degree of teratozoospermia affected the PR in hMG-stimulated IUI cycles and a normal morphology value of 10% in the fresh semen distinguished couples with good and poor outcomes. In contrast, the number of motile sperm inseminated did not significantly influence IUI outcome.

The effect of oral contraceptives on hormone profiles of oligomenorrheic adolescent cycles.

Nineteen adolescent girls with oligomenorrhea were studied to evaluate the effect of oral contraceptives (OCs) on hormone profiles, and 19 adolescent girls with regular menstruations served as control subjects. Serum levels of luteinizing hormone and androgens were higher in the oligomenorrheic girls than in the regularly menstruating girls. During the OC treatment the hormone levels of the oligomenorrheic girls decreased, approaching those of the control subjects. During follow-up cycle immediately after stopping the OCs the hormone levels increased rapidly, but in the oligomenorrheic girls the levels of luteinizing hormone, androstenedione, total and free testosterone were still significantly lower at the end of the post-treatment cycle than during the luteal phase of the pre-treatment cycle. The frequency of ovulation decreased to the same magnitude as reported in adults after discontinuation of OCs. No post-pill amenorrhea existed in either group of adolescents.

[Prevention of teenage pregnancy]. / Teini-ikäisten raskauden ehkäisy.

PIP: Because the sexual activity of teenagers has increased, birth control is important to emphasize in this age group. The success of pregnancy prevention can be measured by the number of abortions, which has remained relatively stable in the 1980s, following a decrease of 11-16% in the late 1970s in Finland. Use of condoms as a method of birth control has the added benefit of protecting against infectious diseases, such as chlamydia and AIDS. However, combination pills are the most recommended option for young people. Mini-pills and capsules tend to cause menstrual problems among teenagers. Use of spermicides and diaphragms appear to have little appeal with youth. The IUD is not a good method of prevention due to increased risk of infection. Post coital prevention should be included in sex education, but this is likely to be a very transient method. Health care workers need to emphasize confidentiality in activities related to prevention of teenage pregnancy. It would also be beneficial for schools to provide counseling as part of their sex education program.^ieng

Serum sex hormone concentrations in adolescent secondary amenorrhoea.

The hormone concentrations of 17 amenorrhoeic adolescent girls, with no apparent environmental factor associated with the secondary amenorrhoea, were evaluated. 28 regularly menstruating adolescent girls served as controls. The clinical characteristics of both groups were similar, except that the amenorrhoeic girls showed clinical signs of androgenicity significantly more often than the regularly menstruating group. The concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, oestradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were determined in weekly blood specimens from the amenorrhoeic girls and during one menstrual cycle from the regularly menstruating girls. The amenorrhoeic girls had significantly higher concentrations of LH, androstenedione and free testosterone than the regularly menstruating girls. The LH/FSH ratio was significantly higher in the amenorrhoeic group than in the control group. The SHBG concentrations were significantly lower in the amenorrhoeic group than in the regularly menstruating group. Evaluation of the clinical signs of androgenicity combined with LH and androgen measurements seems important in the investigation of adolescent menstrual disorders.

Ovarian stimulation during gonadotropin treatment after hCG administration monitored by ultrasound and serum estradiol and progesterone.

Ovarian volumes, measured with ultrasound, and serum estradiol and progesterone concentrations were studied during gonadotropin treatment cycles 1 week after hCG administration in 23 patients, of whom nine had polycystic ovarian syndrome (PCO), eight oligomenorrhea or amenorrhea corresponding to WHO group II (OMG), and six hypogonadotropic amenorrhea corresponding to WHO group I (HGT). The ovarian volumes were greater in the PCO and HGT groups than in the OMG group. The serum estradiol and progesterone concentrations correlated more closely with ovarian volumes in the HGT group than in the PCO and OMG groups. The present study failed to demonstrate a lower risk of hyperstimulation in the HGT group in comparison with the PCO and OMG groups. Six patients conceived, and ovarian volumes were greater and serum progesterone concentrations higher during conceptual cycles than during nonconceptual cycles.

[Hormone treatment in the climacteric]. / Hormonbehandling i klimakteriet.

To improve the quality of life among women during the three decades following the menopause, every effort should be made to prevent the adverse effects of ageing. Broad joint initiatives, involving various disciplines such as, cardiology, urology, oncology, orthopaedics and gynaecology, are needed to optimise medical care during the climacteric. Oestrogen-progesterone treatment is the most important means currently available for the prevention of postmenopausal problems. This form of hormone therapy also appears to provide protection against osteoporosis and cardiovascular disease.

Reduced short-term variability of fetal heart rate in association with maternal hyperglycemia during pregnancy in insulin-dependent diabetic women.

The differential index, which describes the short-term component of fetal heart rate variability, and maternal blood glucose levels were measured 109 times in 19 insulin-dependent diabetic mothers in the second half of gestation. An abnormal differential index was observed more often with maternal hyperglycemia (11/45) than with normoglycemia (5/64). A significant negative linear correlation was found between the differential index and the blood glucose level of the mother.

Endocrine and clinical effects of spironolactone in female hyperandrogenism.

In a double-blind cross-over study, 24 hyperandrogenic women were treated for three months at a time with either spironolactone 100 mg or placebo daily from the 5th to the 21st days of the menstrual cycle. Spironolactone had a slight but statistically insignificant effect on hirsutism when compared with placebo. Slightly more regular menstruation and better follicular growth was noted during spironolactone treatment. Ovulation (defined as a day 21 serum progesterone level of more than 10 nmol/l) occurred in only 12% of spironolactone cycles, as against 28% of placebo cycles. Spotting occurred in one-third of the spironolactone cycles. No significant differences were found between spironolactone and placebo cycles in serum levels of LH, FSH, prolactin, estradiol, progesterone, androstenedione, total testosterone, sex-hormone binding globulin (SHBG), unbound testosterone, dehydroepiandrosterone sulphate (DHEAS), cortisol, potassium and sodium. The average ovarian volume was 13.0 (5.7-21.8) cm3, and no significant differences were found between treatment and placebo cycles. No significant effect of spironolactone could be demonstrated on androgen secretion and the incidence of ovulation.

Serum sex hormone levels in adolescent girls with polymenorrhoea.

The hormone levels of 13 polymenorrhoeic adolescent girls were evaluated. Twenty-eight adolescent girls with regular menstruation served as controls. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, oestradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulphate, and sex hormone binding-globulin were determined in blood samples obtained over one menstrual cycle. In girls with polymenorrhoea the frequency of ovulation was significantly lower than in the control group as estimated on the basis of the progesterone level five days before the onset of menstruation. Low progesterone and oestradiol levels during the late part of the cycle were the main abnormalities of polymenorrhoeic adolescent girls. No differences in the other hormonal parameters were found. The duration of menstrual bleeding was similar in both groups.

Pregnancy resulting from intracytoplasmic injection of spermatozoa from a frozen-thawed testicular biopsy specimen.

A testicular biopsy specimen was taken in connection with scrotal exploration of a healthy 35 year old man who had azoospermia. Bilateral severe scarring of unknown aetiology was found in the exploration, and no epididymal spermatozoa could be obtained. Spermatozoa from the fresh biopsy specimen were used for intracytoplasmic sperm injection (ICSI) on the same day. Two-embryo transfer resulted in biochemical pregnancy. The rest of the biopsy specimen was frozen as small pieces of tissue using glycerol as a cryoprotectant. ICSI was then performed with spermatozoa prepared from the frozen-thawed tissue. One embryo was obtained and transferred. The transfer resulted in pregnancy, and a living fetus was seen in ultrasound scans at the seventh and 16th weeks of pregnancy. It is possible to avoid repeated testicular biopsies by using cryopreservation of testicular tissue.