Changes in male hormone profile after occupational organophosphate exposure. A longitudinal study.

There is a growing concern about the endocrine effects of long-term, low-level exposure to organophosphate (OP) compounds. Studies on experimental animals have found that OP pesticides have an impact on the endocrine system and a few clinical and epidemiological studies have also shown that OPs may affect the male hormone profile, although results are inconsistent. We have evaluated the effect of exposure to OP pesticides, measured through urinary levels of six dialkylphosphate (DAP) metabolites, on male hormone profile in 136 floriculture workers from the State of Mexico and Morelos during two agricultural periods with different degree of pesticide exposure. Generalized estimated equations (GEE) models were developed and adjusted for several potential confounders, including PON1 enzyme activity, as a biomarker of susceptibility, and serum levels of p,p'-DDE, a metabolite of the pesticide DDT widely used in Mexico until 1999 for control of agricultural pests and malaria. Exposure of male floriculture workers to OP pesticides was associated with increased serum levels of follicle-stimulating hormone (FSH) and prolactin and with decreased serum testosterone and inhibin B levels. Among all DAPs tested, only DETP was inversely associated with luteinizing hormone (LH). Estradiol showed a marginally significant positive trend with DEP and DETP derivatives. In conclusion, OP pesticides may have an impact on the endocrine function because of their potential to modify the male hormone profile as a function of the type of pesticide used as well as the magnitude of exposure.

Effects of levonorgestrel implant upon TSH and LH levels in male infants during lactation.

OBJECTIVES: The objective of the study is to evaluate the effects of levonorgestrel transferred through breast milk on thyroid stimulating hormone (TSH) and luteinizing hormone (LH) levels in full breast-fed infants. METHODS: Forty healthy postpartum women and their male newborns were recruited for the study. Women were randomly allocated to two study groups: Group 1, IUD users and group 2, Norplant users. Blood and milk samples were collected on the day of IUD or Norplant insertion and 3 and 6 months later for TSH and levonorgestrel measurements. RESULTS: The results disclosed a significant decrease in TSH levels, and a negative relationship between LNG levels and TSH concentration in breast feeding infants at 3 months after implant insertion. The lowest TSH levels were observed at 6 months in the women from group 2. CONCLUSIONS: The overall data indicate that the LNG levels transferred to fully breast-fed infants through breast milk from Norplant users significantly modified their TSH levels.

Latin american experience with two low-dose oral contraceptives containing 30 microg ethinylestradiol/75 microg gestodene and 20 microg ethinylestradiol/150 microg desogestrel.

The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel with a preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilean group (95% confidence limit, +/- 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, +/- 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.

Mesigyna once-a-month combined injectable contraceptive: experience in Latin America.

A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.

Acceptability of two spermicides in five countries.

Data from a large, international, multicenter, randomized trial were analyzed to compare the acceptability of two nonoxynol-9 spermicide preparations. Women who wished to use a spermicide for contraception were randomly assigned to use either a foaming tablet (n = 383) or a nonoxynol-9 film (n = 382) for 28 weeks as their only method of contraception. Participants completed questionnaires about acceptability of the assigned product 4 weeks after admission and at discontinuation. Women in both groups had very favorable opinions of the spermicide. The proportion of women who said that they liked their assigned product very much was 50% in the tablet group and 55% in the film group. Significantly more women in the film group rated the spermicide difficult to insert and stated that the product stuck to the finger during insertion. More women in the tablet group said that the product was messy and that, at least once, it did not dissolve. In both groups, liking the product was significantly associated with consistency of use, but not with subsequent pregnancy. Participants' male partners had little influence on participants' opinions about, or use of, the spermicides. Although previous analyses showed that both spermicides are associated with high pregnancy rates, they are both highly acceptable to most women.

PIP: This study compares the acceptability of two nonoxynol-9 spermicide preparations in Mexico, Ecuador, Guatemala, Ghana and the US. A total of 765 women (383 using a foaming tablet and 382 using nonoxynol-9 film for 28 weeks) were enrolled. Participants completed a questionnaire about acceptability of the assigned product, 4 weeks after admission and at discontinuation. Result of the trial revealed that women in both groups had very favorable opinions of the spermicide. The proportion of women who said that they liked their assigned product very much was 50% in the tablet group and 55% in the film group. Significantly more women in the film group rated the spermicide difficult to insert and stated that the product stuck to the finger during insertion. More women in the tablet group expressed that the product was messy and that, at least once, it did not dissolve. In both groups, liking the product was significantly associated with consistency of use, but not with subsequent pregnancy. Participants' male partners had little influence on participants' opinions about, or use of, the spermicides. Although previous analysis showed that both spermicides were associated with high pregnancy rates, they were both highly acceptable to most women.

A multicenter comparative study on the efficacy, safety, and acceptability of the contraceptive subdermal implants Norplant and Norplant-II.

In order to assess efficacy, safety, and acceptability of the contraceptive subdermal implants Norplant and Norplant-II in Mexican women, a comparative phase III clinical trial was undertaken in eight clinics across the country. The study involved 1052 women who were followed-up trimonthly for three years. Cumulative pregnancy rates were 0.29% and 0.34% for Norplant and Norplant-II implants, respectively. Similar overall cumulative discontinuation rates were observed at three years: 50.38% for Norplant capsules, and 50.44% for Norplant-II rods. The main method-related reason for termination was endometrial bleeding irregularity which led to discontinuation rates of 11.94% and 11.62% for Norplant and Norplant-II contraceptive systems, respectively. In 15,279 woman-months of experience accumulated with Norplant implants and 14,092 with Norplant-II implants, there were few adverse events reported. No difference was found between the two groups in either difficulty for implants placement and removal or women's discomfort, even though the time required for insertion and removal of Norplant capsules was longer than for Norplant-II rods. It is concluded that during the first three years of use, both implants systems are equally effective, safe, and acceptable.

Effects of oral buserelin on urinary LH secretion in male infants.

In recent years, several potent gonadotropin-releasing hormone (GnRH) analogues have become available for female contraception and one of them (buserelin) has been tested in lactating women. However, the possible effects on infants due to the transference of the analogue through breast milk have not been studied. The present work evaluated the effect of oral buserelin on urinary LH secretion in male infants. A total of 19 healthy full-term boys (aged 2-4 months) were included in the study. Infants received orally a single dose of a GnRH agonist mixed with breast milk. Urine samples were collected prior to, and 4-6 and 24 h after treatment for LH measurement. The results disclosed a significant increase in LH urine level in the sample taken 4-6 h after buserelin administration. Twenty-four hours after GnRH agonist ingestion, the LH level returned to baseline level. The present study demonstrated that GnRH analogue administered orally to infants escapes from gastrointestinal inactivation and induces a significant rise in LH levels 4-6 h after treatment.

PIP: An evaluation of the effects of oral buserelin on urinary luteinizing hormone (LH) secretion in 19 healthy breast-fed male infants 2-4 months of age indicated a need for further research on the effects of this agent on the hypothalamic-pituitary-gonad axis of infants. A single dose of 35 mcg of buserelin from a nasal spray was mixed with 20 ml of breast milk and fed to each infant, followed by a normal breast feed. A significant increase in urinary LH concentrations occurred between baseline (0.6 +or- 0.7 mUI/ml) and 4-6 hours after treatment (1.5 +or- 1.1 mUI/ml); however, 24 hours after agonist ingestion, LH levels returned to baseline levels. These findings suggest that a sufficient quantity of buserelin escapes from the gastrointestinal inactivation to stimulate the infant's pituitary, resulting in LH release. This phenomenon is probably due to an immaturity in the infants' gastrointestinal enzymes function.

Effects of low steroid doses administered in the mid and late follicular phase on the LH surge, ovarian steroids and follicular maturation in eumenorrheic women.

The effects of four low doses of synthetic steroids, administered orally and starting on day 8 (group I) or on day 10 of the menstrual cycle (group II), upon LH surge, ovarian steroidogenesis, follicular maturation and menstrual cycles were studied in 10 eumenorrheic women. The results revealed that the day before the LH surge, the highest level of estrone-3-glucuronide was observed in both groups. Twenty-four hours after the last dose, the maximum urinary LH levels were recorded in groups I (day 11), and II (day 13). Pregnanediol-3 alpha glucuronide remained low during the study in group I, whereas in group II a gradual rise of this hormone starting on day 13 was registered and the highest level was found at day 21 of the menstrual cycle. Follicular maturation and ovulation were observed only in women from group II. Short and normal length cycles were recorded in groups I and II, respectively. In summary, low doses of exogenous synthetic steroids administered on day 8, but not on day 10 of the cycle, inhibit follicular maturation and ovulation.

A comparative study on the return to ovulation following chronic use of once-a-month injectable contraceptives.

A comparative study was undertaken involving 21 Mexican women who discontinued the use of medroxyprogesterone acetate 25 mg plus oestradiol cypionate 5 mg (Cyclofem) and norethisterone enanthate 50 mg plus oestradiol valerate 5 mg (Mesigyna) to assess the time required for the return to menses and ovulation. All subjects were exposed to once-a-month injectable contraceptives for two years and were followed for 120 days after the last injection. The urinary concentration of oestrone glucuronide and pregnanediol glucuronide was determined daily in all subjects beginning one month after the last injection. The results disclosed that ovulatory cycles were documented after 120 days of the last injection in six women of each studied group. Similar endometrial bleeding patterns were observed in both groups, indicating that the two drugs have alike pharmacokinetic and pharmacodynamic effects.

PIP: At the family planning clinic of the medical school in Coahuila, Mexico, providers recruited 11 volunteers requesting an injectable contraceptive into Group I (Mesigyna: 50 mg norethisterone enanthate + 5 mg estradiol valerate) and 10 similar volunteers into Group II (Cyclofem: 25 mg medroxyprogesterone acetate + 25 mg estradiol cypionate). After they used the injectables continuously for two years, researchers followed them for 120 days after the last injection. Early morning urine samples were taken every day between day 30 and day 120 after the last injection to measure estrone glucuronide and pregnanediol glucuronide. Researchers also measured the urinary luteinizing hormone level. Normal ovulatory cycles returned within the first to third month after injection in six users from each group. In fact, all but one woman in the Group I had a normal ovulatory cycle during the first month. The other woman had a normal cycle during the second month. During months 1, 2, and 3, the numbers of women in group II who had a normal ovulatory cycle were 3, 2, and 1, respectively. The two groups did not have significant differences in the first bleeding-free interval (51 for Group I vs. 43 for Group II) and in the total number of bleeding/spotting days (11 vs. 14). These findings suggest that long-term use of these injectable contraceptives did not cause chronic inhibition of the hypothalamus-pituitary-ovarian axis and that the ovarian function and the endometrial bleeding patterns returned to normal similarly in both groups. Thus, national family planning programs in developing and developed countries may want to consider offering them as part of the contraceptive mix.

Effects of storage and temperature upon soft jelly capsules containing nonoxynol as spermicide.

Recently, adverse effects of long periods of storage and high temperature on physical characteristics of the soft jelly capsule wall were observed. In the present study, the effects of both parameters upon the mean rupture time of the capsule, and the release of the active compound were evaluated in vivo in 40 women. The results disclosed that the storage for long time and the exposure of the capsules to high temperatures, delays significantly the mean rupture time and the release of the active compound. A rapid distribution, adequate storage, as well as a delay of intercourse after vaginal insertion of the device are suggested.

PIP: In Coahuila, Mexico, 20 women vaginally inserted soft jelly capsules containing the spermicide nonoxynol-9 which had been stored for 90 days at 25-30 degrees Celsius (group I), and 20 more women inserted capsules of the same type which had been stored in an incubator for 90 days at 45 degrees Celsius (group II). All 40 women inserted the capsules during days 12-14 of the menstrual cycle to avoid physiological changes of vaginal humidity during the cycle. At the end of each study period (2-13 minutes), rupture/nonrupture and weight of the capsules were recorded. A loss of more than 15% of the capsule's weight constituted release of nonoxynol-9. The time for the capsule to rupture ranged from 4 to 12 minutes for group I and from 6 to 13 minutes for group II. The mean rupture time was greatest for those capsules stored at the higher temperature (i.e., group II) (10.2 vs. 5.6 minutes; p 0.001). The mean release time was also greatest for group II (12.1 vs. 6.7 minutes; p 0.02). Thus, long storage and high temperature delayed the minimum time for capsule rupture in the vagina by 4-6 minutes. Capsules stored for a long time and at a high temperature had a higher wall consistency than their counterparts. Capsules stored at a high temperature had a harder consistency than those stored at a lower temperature. These findings suggest the need to rapidly distribute capsules, to store them under controlled temperature, and to delay intercourse after insertion for more than 10 minutes.

Review of ovulation return upon discontinuation of once-a-month injectable contraceptives.

Once-a-month combined injectable preparations draw their contraceptive efficacy from continuous ovulation suppression. When their use is discontinued, ovulation resumes within a few weeks or a few months, depending on the formulation. After use of the dihydroxyprogesterone acetophenide 150 mg/estradiol enanthate 5 mg combination for one to two years, ovulation returns in most subjects 3-4 months after discontinuation of treatment. Similarly, recent data show that after 2-year use of the depot-medroxyprogesterone acetate 25 mg/estradiol cypionate 5 mg or the norethisterone enanthate 50 mg/estradiol valerate 5 mg combination, approximately 70% women have resumed ovulation by the third month post-treatment. This is shorter than the time for return of ovulation experienced by ex-users of progestogen-only injectable contraceptives.

PIP: This paper reviews the progress made in the determination of ovulation and specifically addresses the effects of returning ovulation after discontinuance of once-a-month injectable contraceptive preparations. Correlation between ovulation and the hormones estrogen, progesterone, and luteinizing hormone (LH) is well documented. It has served as the basis for many studies on determining ovulation mid-point and in evaluating the efficacy, safety, and time of returned ovulation when using various contraceptive methods and preparations. Current monthly injectable contraceptive formulations are discussed and used as comparison for the new generation injectables. New generation contraceptives in this study are preparations (combinations) of several compounds. The depot microcrystalline form of medroxyprogesterone acetate (DMPA) in combination with estradiol cypionate (E2-Cy) was studied. The authors conclude that these initial studies on the new generation combination monthly injectables indicate that these new contraceptives are highly effective in inhibiting ovulation, as well as allowing for predictable return of ovulation.

Safety and efficacy of a combined oral contraceptive: gestodene 75 micrograms plus ethinyl estradiol 30 micrograms in Mexican women.

An open prospective clinical trial designed to evaluate the efficacy and safety of the combined hormonal oral contraceptive (OC) containing 75 micrograms gestodene plus 30 micrograms ethinyl estradiol was undertaken in a Mexican population. Sixty-nine healthy women of reproductive age took part in the study for a total of 627 woman-months of observation. The combination of gestodene and ethinyl estradiol proved its effectiveness in preventing pregnancy during the study. Side-effects were minimal and regular endometrial bleeding patterns were observed during one year of continuous use of this OC preparation. The discontinuation rate for medical reasons was 11.6% at one year. Among a sample of 10 women, the gestodene/ethinyl estradiol combination did not induce significant changes in the serum concentration of total cholesterol and LDL cholesterol after 12 months of continuous administration. An increase in serum triglycerides and HDL cholesterol was observed; this effect could be attributed to a lack of androgenic and/or the intrinsic estrogenic behavior of gestodene. It can be concluded that this preparation is highly effective as a combined oral contraceptive; it is well tolerated and might offer some advantages with respect to other oral contraceptive combinations in its short- and medium-term impact on lipid metabolism.

Comparative study on the efficacy and acceptability of two contraceptive pills administered by the vaginal route: an international multicenter clinical trial.

The efficacy and acceptability of two widely used oral contraceptive tablets, one containing 250 mg levonorgestrel and 50 micrograms ethinyl estradiol and the other containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, administered by the vaginal route were compared in 1055 women studied over 12,630 woman-months of vaginal contraceptive pill use. This multicenter clinical trial was performed in nine countries of the developing world by the "South to South Cooperation in Reproductive Health," an organization founded by scientists from the Third World working in the area of reproductive health, and the study was developed and coordinated by one of these centers. The findings of this study confirm the efficacy of both these tablets when administered by the vaginal route. Involuntary pregnancy rates at 1 year of 2.78 for subjects in the levonorgestrel group and 4.54 for subjects the desogestrel group showed no statistically significant difference between the two groups. However, total discontinuation rates of 47.01 for subjects in the levonorgestrel group and 56.33 for subjects in the desogestrel group showed a statistically significant difference between the two groups, and discontinuation rates attributable to prolonged bleeding of 0.6 for subjects in the levonorgestrel group and 3.2 for subjects in the desogestrel group were also significantly higher in the group of subjects using the desogestrel vaginal contraceptive pill. Blood pressure remained at admission values throughout treatment. A statistically significant weight increase from admission values occurred in both groups of subjects.

PIP: Efficacy and acceptability of 2 combined oral contraceptive pills administered vaginally are summarized. This is the 1st collaborative trial published by the South to South Cooperation in Reproductive Health. 1055 women participated in 12,630 cycles, in 9 countries, from June 1988 to May 1991. The pills were commercially available tablets containing 50 mcg ethinyl estradiol and 250 mg levonorgestrel (Schering AG, Sao Paulo, Brazil), or 30 mcg ethinyl estradiol and 15 mcg desogestrel (Organon, Sao Paulo, Brazil). Subjects were aged 17-39 younger and of lower parity from Mexico and Dominican Republic and older from Egypt and China. All had at least 1 pregnancy. 675 participated for 6 months, 470 for 1 year, 364 for 18 months, and 210 for 2 years. The 1-year discontinuation rate averaged 47.01% for the levonorgestrel group and 56.33% for the desogestrel group (p = 0.0061); 2-year discontinuation rates were 48.01% and 69.36, respectively, explained in part by higher involuntary pregnancy rates and prolonged bleeding rates in the desogestrel group. The most common medical reasons for stopping contraception were unplanned pregnancy, vaginal or vulval irritation, nausea, vaginal discharge and headache. Vaginal irritation was reported by 1%, 9 in each group. There were 32 pregnancies, 14 in the levonorgestrel and 18 in the desogestrel group. 17 were in missed pill cycles and the rest were method failures, 6 in the levonorgestrel group and 9 in the desogestrel group. The Pearl index varied from 0 in Nigeria to 12.24 in Mexico, and was 2.45 for levonorgestrel vs. 3.74 for desogestrel. There was a wide variation in discontinuation rates by center: Brazil and China had few, while many women from Dominican Republic, Mexico and Zambia left the study. Bleeding problems were common complaints, more so in the desogestrel group. There were 363 women with intermenstrual bleeding (only once in 80%), 148 with spotting (only twice in 65%). Bleeding duration was significantly less in pill cycles than baseline, pressure. Women gained an average of 1 kg over 2 years, more in the desogestrel group. The pregnancy rate of 2.78 is within the range reported for levonorgestrel rings.

Assessment of a new modified soft jelly capsule containing nonoxynol as spermicide contraceptive.

The mean rupture time, after its vaginal insertion, of a new modified soft jelly capsule containing nonoxynol-9 (DF-486) was investigated in 40 women. The subjects were randomly allocated to 8 study groups. The capsules remained in the vagina from 2-13 minutes. Vaginal infection, vaginal dryness, and multiparity, were recorded. Capsule rupture was not observed at minute 2; 20% of capsules that remained in the vagina 3 minutes suffered rupture, as did 80% of capsules that remained 4, 5 and 7 minutes, and 100% of those remaining 9 minutes or more. The mean rupture time of the studied capsules was 8.2 minutes with 95% confidence limits of 6.2 and 8.8 minutes. At minutes 2-7, vaginal infection, dryness and tone diminution probably accounted for lack of rupture; after minute 7, these factors did not influence capsule rupture.

Immature spermatogenic cells and leucocytes in normal and abnormal semen.

The frequency and ranges of the immature germinal cells (IGC) were established in 286 semen analyses from normozoospermic (group I), oligozoospermic (group II), and azoospermic (group III) subjects. The mean total count of IGC was greater between men from group I than between participants from groups II and III. Scd spermatids were the cells most frequently observed and the spermatogonia the most unfrequently seen. Sab and Scd spermatids were the most common cells observed in group I, whereas Scd and primary spermatocytes were the most common in group II, and Scd and secondary spermatocytes were the most common in group III. Correlation was found between sperm concentration and the IGC total count. Significant differences were not found when epithelial cell and leucocyte concentrations were compared between groups.

[Effectiveness and safety of a new combined oral contraceptive containing 75 micrograms gestodene and 30 micrograms ethinyl estradiol in Mexican women]. / Efectividad y seguridad de un nuevo preparado anticonceptivo oral combinado 75 mcg gestodeno mas 30 mcg etinilestradiol en mujeres mexicanas.

PIP: 69 healthy Mexican women using a new oral contraceptive (OC) containing 75 mcg of gestodene and 30 mcg of ethanol estradiol participated in a prospective study of the safety and efficacy of the method. All participants were evaluated on the s cycle day before beginning use and were questioned monthly about side effects and menstrual bleeding. 10 of the women were evaluated for cholesterol and triglyceride levels before use and after 4 and 8 months. The average age of the participants at admission into the study was 23.4 years. There were no pregnancies in 613 woman-months of use. The average blood pressure was 113.8 + or - 6.9 over 76.7 + or - 7.0 before use and 112.6 + or - 9.2 over 73.8 + or - 7.8 after 12 months of use. The average weight was 55.9 + or - 9.6 kg before use and 55.5 + or - 8.8 after 12 months of use. In the 1st treatment cycle 8 women reported spotting and 3 reported intermenstrual bleeding; the number reporting these signs gradually declined. The number reporting side effects was small and declined after the 1st treatment cycle. Dysmenorrhea declined significantly after the 1st cycle. The crude rate of termination was 44.9% after 1 year. 8 women (11.6%) terminated method use for reasons related to the method, including 2 for nausea and vomiting, 1 for nausea and dizziness, 2 for amenorrhea, and 1 each for intermenstrual bleeding, spotting, and increased blood pressure. Among the 10 women whose lipid and lipoprotein levels were tested, the average levels before and after 8 months respectively were 162.5 + or - 27.0 and 182.3 + or - 35.8 for total cholesterol, 86.5 + or - 29.5 and 120.0 + or - 45.0 for triglycerides, 45.7 + or - 9.3 and 60.6 + or - 6.5 for HDL cholesterol. In general these changes were not significant despite the tendency to increase especially of the triglycerides. The method thus appears to offer advantages for temporary fertility control among Mexican women.^ieng

Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin.

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.

Comparative trial between two soft jelly capsules containing nonoxynol as spermicidal contraceptives.

The rupture time of two types of soft jelly capsules (treated and non-treated) containing Nonoxynol-9 after its vaginal insertion was investigated in 96 women. Subjects were allocated in four study groups: Group I (n = 24), women with clinical vaginal infection; Group II (n = 24), subjects without vaginal infection; Group III (n = 24), patients with vaginal infection; and Group IV (n = 24), women without vaginal infection. Groups I and II received the treated capsules, and Groups III and IV the non-treated capsules. The capsules remained in the vagina for 2.5 to 5 minutes. The weight of the capsules was measured before insertion and after their extraction. Additionally, vaginal pH and distribution of the compound were assessed. The results disclosed that in Groups I, III and IV, the capsules ruptured within 2.5 minutes, whereas in Group II the rupture did not occur until 3 minutes. The largest number of non-ruptured capsules was observed in Group II. The major capsule weight loss occurred at minute 5 in most of the groups. The conditions currently observed in cases of non-ruptured capsules were: alkaline pH, multiparity and vaginal dryness. The vaginal distribution of the compound was observed at its upper portion. In women with vaginal infections, there were more cases of rupture and a significant weight loss between the treated capsules than the non-treated capsules. Further postcoital tests are required to assess its effectiveness.

PIP: The rupture time of 2 types of soft jelly capsules (treated and non-treated) containing Nonoxynol-9 after its vaginal insertion was investigated in 96 women in Mexico. Subjects were allocated in 4 study groups: Group I (n=24), women with clinical vaginal infection; Group II (n=24), subjects without vaginal infection; Group III (n=24), patients with vaginal infection; and Group IV (n=24), women without vaginal infection. Groups I and II received the treated capsules, and Groups III and IV the non-treated capsules. The capsules remained in the vagina for 2.5 to 5 minutes. The weight of the capsules was measured before insertion and after their extraction. Additionally, vaginal ph and distribution of the compound were assessed. The results disclosed that in Groups I, III and IV, the capsules ruptured within 2.5 minutes, whereas in Group II the rupture did not occur until 3 minutes. The largest number of non-ruptured capsules was observed in Group II. The major capsule weight loss occurred at minute 5 in most of the groups. The conditions currently observed in cases of non-ruptured capsules were: alkaline ph, multiparity and vaginal dryness. The vaginal distribution of the compound was observed at its upper portion. In women with vaginal infections, there were more cases of rupture and a significant weight loss between the treated capsules than the non-treated capsules. Further postcoital tests are required to assess its effectiveness.

Endocrine and biochemical studies in a 46,XY phenotypically male infant with 17-ketosteroid reductase deficiency.

A 46,XY phenotypically male patient with 17-ketosteroid reductase deficiency is described. The patient was a 6-month-old infant who presented with micropenis and bilateral cryptorchidism. Baseline plasma levels of testosterone (T), delta 4-androstenedione (delta 4A), and 5 alpha-dihydrotestosterone (5 alpha-DHT) were within the normal range [patient: 0.17 (T), 0.12 (delta 4A), and 0.032 (5 alpha-DHT) ng/ml; normal infants: 0.03-0.55 (T), 0.14-0.45 (delta 4A), and 0.01-0.23 (5 alpha-DHT) ng/ml]. hCG administration induced a significant rise in plasma delta 4A levels (up to 8.39 ng/ml) and a slight increase in T and 5 alpha-DHT levels. The delta 4A/T ratios before and during the hCG challenge were 0.86 and 55.61, respectively (controls: 0.83 and 0.13). Incubation of genital skin-derived fibroblasts from the patient with either [3H]T or [3H] delta 4A revealed normal formation of delta 4A from T and diminished conversion of delta 4A to T. The development of a male phenotype despite both a testicular and peripheral 17-ketosteroid reductase deficiency is difficult to explain. It is possible that the fetal testes were the source of sufficient amounts of T during the early periods of embryonic life, and that late onset of the enzyme deficiency prevented the development of completely normal male genitalia. The in vitro finding of normal T to delta 4A conversion by the mutant fibroblasts suggests that in this particular tissue 17 beta-reduction and dehydrogenation of androgens are mediated by two isoenzymes with distinct substrate and/or cofactor specificities.

Endocrine and immunogenetic evaluation of an XX male infant with perineoscrotal hypospadias.

To clarify the origin of the genital ambiguity occasionally associated with the XX male syndrome, a series of endocrinological studies were undertaken in an affected 6 months old infant with perineoscrotal hypospadias. The patient fulfilled all the diagnostic criteria of the syndrome: the testes were descended bilaterally, the Mullerian derivatives were absent, the 46,XX chromosome complement was ascertained in different cell lines, and male levels of H-Y antigen were detected in cultured skin fibroblasts. Circulating gonadotrophin levels and pituitary LRH responsiveness were within normal limits for the age group. Serum testosterone (T) levels were normal, and gonadal stimulation with hCG caused a significant rise on serum T. Incubations of [3H]T with fibroblasts from genital skin revealed normal activity of steroid 5 alpha-reductase. Moreover, normal concentrations of thermostable cytosol androgen receptors were revealed in cultured fibroblasts. Altogether the results indicated that ambiguity of the external genitalia in this patient was the result of neither abnormal T biosynthesis, peripheral A-ring T reduction, nor androgen intracellular specific binding, and suggested that the nature of the incomplete virilization could be a non-endocrine independent event associated to this disorder. The data are also consistent with the notion that testicular impairment observed in adult XX males develops later in life.