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Biomedical subjects

I H Thorneycroft

Publications and source records attributed to I H Thorneycroft.

At least 19 recordsLinked to original sources
PubMed2002

Yasmin: the reason why.

Oral contraceptives have been available for a little over 40 years and, during that time, many different formulations have been introduced. There have been dramatic dosage reductions of both the estrogen and progestogen components and various progestogens have been introduced over time. The properties of most progestogens used in oral contraceptives are very similar, differing mainly in potency. Oral contraceptives with progestogens having new and unique properties are needed. World-wide, around 20-30% of women of childbearing age use oral contraceptives and their use declines after the age of 35 years, with an accompanying increase in the rates of unintended pregnancy and elective termination. Incorrect use likewise gives rise to high unintended pregnancy rates. Use in Europe is higher than in other regions. Discontinuation because of unwanted effects and misperceptions is very common. Common misperceptions that prevent women from initiating oral contraceptive use are weight gain, cancer risks and that bleeding indicates a significant problem. Unwanted effects that commonly give rise to discontinuation are bleeding, nausea, weight gain, mood changes, breast tenderness and headaches. Discontinuation rates are high, particularly in the first year, and adolescents have the highest rates of discontinuation. Correct consistent use must be encouraged by taking pills at a regular time each day and by reinforcing that bleeding and other unwanted effects are not medically serious. Reinforcement of the non-contraceptive health benefits is very important and it needs to be emphasized that long-term use enhances these non-contraceptive benefits. Most non-contraceptive benefits are due to the progestogen component and its inhibition of ovulation. The new drospirenone-containing oral contraceptive (Yasmin, Schering AG, Berlin, Germany) offers the traditional non-contraceptive benefits; however, due to its unique antimineralocorticoid and antiandrogenic properties, new and unique benefits have been observed. Acne is well controlled, as would be expected from its inhibition of ovulation, antiandrogenic activity and lack of attenuation of the estrogen-mediated increase in sex hormone binding globulin. Its antimineralocorticoid activity gives rise to a reduction in fluid-related symptoms. The oral contraceptive containing 3 mg drospirenone with 30 microg ethinylestradiol DRSP/EE) has excellent efficacy since drospirenone is a potent progestogen, the corrected Pearl index being 0.09. This index is lower than those of many other oral contraceptives. Cycle control is excellent and comparable to that experienced with other oral contraceptives. A significant and consistent weight loss was seen with DRSP/EE compared to a reference preparation containing desogestrel. Day-to-day compliance and the duration of intake of an oral contraceptive are dependent on the woman's satisfaction with the pill she is taking. DRSP/EE meets these expectations and, with its new and unique non-contraceptive benefits, offers a real new choice to women.

Adolescent↗
PubMed1999

Cycle control with oral contraceptives: A review of the literature.

Comparing the degree of cycle control provided by various oral contraceptives is problematic. The inherent limitations, small demonstrated differences, and differing methods of data presentation characteristic of these trials support the conclusion that it is almost impossible to compare the bleeding patterns of one preparation with those of another. Chlamydial infection, smoking, and inconsistency of use are factors that have significant effects on rates of spotting and breakthrough bleeding. Clinicians must alert patients to the possibility of intermenstrual bleeding and educate them with regard to the importance of continued, consistent oral contraceptive use to minimize those problems among pill users in their practices.

Chlamydia Infections↗
PubMed1999

Update on androgenicity.

The development of a new generation of progestins deemed less androgenic than their earlier counterparts has led to a number of misconceptions regarding their possible benefits in combination oral contraceptives. All combination oral contraceptives are beneficial for treating such androgenic conditions as acne and hirsutism. The only expressed androgenic effect of some first- and second-generation combined oral contraceptives are changes in plasma lipid and lipoprotein levels. However, the overall effect of today's low-dose oral contraceptives is largely lipid neutral, and human and monkey studies have shown that oral contraceptive use is associated with reduced, not increased, atherosclerosis rates. Myocardial infarction rates are not increased among oral contraceptive users, except among those who are heavy smokers.

Acne Vulgaris↗
PubMed1999

Effect of low-dose oral contraceptives on androgenic markers and acne.

Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.

Acne Vulgaris↗
PubMed1999

Analysis of in vitro migration patterns of human spermatozoa by a petri dish-based horizontal column.

Spermatozoa are required to travel a considerable distance in vivo to meet the oocyte at the fertilization site. However, none of the existing in vitro tests critically evaluates migration of sperm to assess their potential of reaching the oocyte. On the other hand, an in vivo model is not suitable for this type of study because of ethical and technical constraints. In the present study we utilized a horizontal column technique to analyze sperm migration. Migratory characteristics of fresh, unwashed semen sperm and sperm undergoing various treatments were examined in vitro using a Petri dish-based horizontal fluid column. The procedure involved loading a sperm sample into the column and determining sperm concentration, motility, and viability at different column segments for different migration durations (6, 12, 24, 48, and 72 h). All sperm samples produced an exponential migration pattern in all durations of migration. Propagation along the column edge, tendency to exit from the column, and hiding in the blind pouches were some of the important characteristic features exhibited by the migratory sperm. Variations in migration patterns were documented among semen donors, between fresh and frozen semen, and between washed and unwashed sperm. Prolonged postejaculation time diminished migratory potential. The recovery of sperm in the column end was independent of seminal variables with the exception of oligozoospermia. These observations suggest that the Petri dish-based horizontal column is effective for analyzing sperm migration characteristics for prolonged periods. The potential of this migration assay in predicting the in vivo potential of spermatozoa to reach the fertilization site will be worth exploring.

Humans↗
PubMed1999

Protecting the endometrium. Opposing the hyperplasia/malignancy potential of ERT.

Many trials have examined the clinical and histologic effects of various hormone replacement therapy combinations with the objective of minimizing the incidence of hyperplasia and the potential for subsequent development of adenocarcinoma. Reviewing the results of these trials, it appears that high-dose, long-term progestogen therapy is effective in protecting the endometrium, with duration having a greater impact than dose. Among women given 0.625 mg conjugated equine estrogen (CEE), sequential regimens should include 5 or 10 mg medroxyprogesterone acetate (MPA) or 200 mg micronized progesterone for 12 days or more. Continuous combined regimens require 2.5-5 mg MPA. With women who are taking 1.25 mg CEE the data are less clear, but recommendations include administration with 10 mg MPA for 12-14 days or 5 mg MPA continuous combined therapy.

Adult↗
PubMed1999

Vaginal bleeding patterns in women receiving hormone replacement therapy. Impact of various progestogen regimens.

Postmenopausal bleeding is more prevalent than was previously thought, occurring in women regardless of whether or not they are on hormone replacement therapy. While estrogen-only regimens have been used for several beneficial effects, bleeding patterns associated with these regimens can be irregular and unpredictable, causing discomfort to the patient as well as increasing the risk of both endometrial hyperplasia and carcinoma. Studies in recent years have examined the effects of estrogen-only regimens as compared to different estrogen-plus-progestogen combination therapies to help regulate and minimize postmenopausal bleeding while providing endometrial protection.

Aged↗
PubMed1998

Time course of hypo-osmotic swellings of human spermatozoa: evidence of ordered transition between swelling subtypes.

The hypo-osmotic swelling test (HOST or HOS test) usually takes into consideration the total HOS response value with no emphasis either on the value of the response subtypes or the response evaluation time. This study investigated the time course of HOS responses and analysed their physiological relevance. Raw semen spermatozoa and Percoll washed spermatozoa were used in the experiment. The morphological changes in the sperm tail were monitored by incubating the spermatozoa in the hypo-osmotic solution for 16 different time periods. The HOS reactive spermatozoa and the type of HOS reaction (swelling subtypes) of the samples subjected to different duration of treatment were identified under a phase contrast microscope. Also the fate of individual spermatozoa in a hypo-osmotic environment were monitored for 30 min. In spermatozoa exposed to a hypo-osmotic solution, the motility lasted usually less than 2 min and motility characteristics were uniquely different from that of the spermatozoa under iso-osmotic conditions. The HOS response development was permanent but the motility loss due to hypo-osmotic shock was reversible up to 1 min of incubation. There was an indication of ordered transition among the HOS swelling subtypes apparently initiating with subtype b destined to c, d, e, f and g. Further, the subtypes a and g showed gradual decrease and increase, respectively, while subtype b showed abrupt initial increase and then gradual decrease. Transition from b to g could be direct or via one or more than one subtypes. Ultrastructure based analysis indicated that HOS response subtypes are the apparent reflection of the differences in the cytoskeletal assembly of the sperm tail and thus may be identifying different physiological variants in the sperm population. These results indicate that shorter incubation is essential to document the kinetics of various HOS responses but the conventional HOS test misses these important HOS features because of lengthy incubation. Since the time course of ordered transition of HOS responses will vary more than the total HOS response in semen of different aetiologies, the importance of HOS response subtypes and response evaluation time should be taken into consideration when applying HOS test.

Cell Separation↗
PubMed1997

Modified guanidinium thiocyanate method for human sperm DNA isolation.

Mammalian sperm chromatin is highly condensed, so isolating DNA from such chromatin can be a formidable task. The procedures that produce high quality DNA from somatic cells fail to yield quality sperm DNA. In this study we have modified the previously used guanidinium method to make it simple and efficient in isolating human sperm DNA. In our method, the lysis buffer contained guanidinium, sodium citrate, sarkosyl, proteinase K and mercaptoethanol. Proteinase K was not used in the original guanidinium method but was included in our protocol. CsCl centrifugation of the lysate, as described in the original procedure, was omitted. Instead, isopropyl alcohol was added directly to the lysis buffer to harvest the DNA. This modified guanidinium method generated high molecular weight DNA while the other two methods resulted in considerable DNA degradation. There was no difficulty in restriction enzyme digestion of DNA prepared by the modified method as revealed by Southern blot analysis. Since the modified guanidinium method is a simple one-step procedure which avoids homogenization, organic solvents, centrifugation and, more importantly, produces degradation-free DNA, it could be the method of choice when DNA from mature germ cells is needed.

DNA↗
PubMed1993

Contraception in women older than 40 years of age.

Women older than 40 years have high rates of unwanted pregnancy and abortion and traditionally have had limited choices of contraception agents. In today's market, oral contraceptives should be considered as should IUDs in properly screened candidates. Sterilization is effective for the couple who knows that they will have no more children. Mechanical methods are effective if used when intercourse tends to be a planned event and infrequent. With the variety of agents available in today's market, there is no reason why the unwanted pregnancy rate and abortion rate of the women older than 40 should not be reduced dramatically.

Adult↗
PubMed1992

Noncontraceptive benefits of modern low-dose oral contraceptives.

Most oral contraceptive formulations in current use contain 50 micrograms or less of ethinyl estradiol and 1 mg or less of the various progestins: norethindrone (0.5-1 mg), norgestrel (0.3-0.5 mg), or levonorgestrel (0.05-0.25 mg) [1]. The new generation of progestins--norgestimate, desogestrel and gestodene--are derived from levonorgestrel, the biologically active enantiomer of norgestrel. These steroids have specific metabolic and pharmacologic activity that allow oral contraception at lower doses than previous progestins. Desogestrel and norgestimate are both prodrugs and must undergo hepatic and gastrointestinal metabolism to become biologically active compounds. Gestodene is immediately and completely bioavailable [2]. For the new formulations containing less than 50 micrograms of ethinyl estradiol, the incidence of complications has decreased. With most of the early medical problems identified, current research can now focus on other aspects of oral contraception such as compliance and OC use failure. Prominent noncontraceptive health benefits have been observed in OC users and represent new directions for future research. When the risk-benefit ratio of OC use is evaluated in healthy women today, it clearly favors the benefits. However, these will not be fully realized without an increase in method compliance.

Blood Coagulation↗
PubMed1992

Endocrine function of granulosa cell tumors in vivo.

Two patients with granulosa cell tumors of the ovary, endometrial hyperplasia, elevated serum estradiol (E2) concentrations and depressed FSH levels were studied preoperatively using intravenous administration of FSH, LH and gonadotropin-releasing hormone. In patient 1, serum E2 increased from a baseline of 72.7 to 116.8 pg/ml 60 min after hCG stimulation, with a peak level of 571.4 pg/ml 96 h after hCG administration; there was a rapid postoperative decline to 16 pg/ml. Ovarian venous E2 on the tumor side was 6,979 pg/ml. In patient 2, E2 increased from a baseline of 91 to 449 pg/ml at 20 h after FSH administration. Intraoperative ovarian venous E2 was 9,788 pg/ml. Inhibin, which was elevated in patient 1 prior to stimulation (736 fmol/ml), peaked 96 h after hCG administration. Ovarian venous inhibin concentration in patient 1 was 2,911 fmol/ml. The baseline inhibin concentration in patient 2 was not elevated (249 fmol/ml), but there was an elevation of inhibin in response to FSH administration (757 fmol/ml), but no response to hCG. Ovarian inhibin concentration was not different between the tumor and contralateral sides in patient 2. Both granulosa cell tumors were responsive to exogenous gonadotropin stimulation. Although only one tumor made significant baseline levels of inhibin, the production of inhibin by both tumors was apparently stimulated by FSH.

Aged↗
PubMed1991

CA 125 levels in abruptio placentae.

The diagnosis of abruptio placentae is frequently difficult despite ultrasonography; additional diagnostic parameters would be useful. Maternal serum CA 125, which is believed to derive from the decidua, is elevated in the first trimester and immediately after delivery when placental separation occurs, possibly because of decidual disruption. Serum CA 125 was measured in 27 patients beyond 20 weeks' gestation who were first seen with vaginal bleeding and in 17 control patients of similar gestational age and labor status. Mean (+/- SD) CA 125 levels were higher (p less than 0.01) among patients with abruptio placentae (105.9 +/- 115 U/ml) than among those with alternate sources of bleeding (13.7 +/- 10 U/ml) or control patients (18.2 +/- 11.7 U/ml). Mean (+/- SD) serum CA 125 levels in seven control patients within 6 hours post partum (194 +/- 80.5 U/ml) were higher than those among patients first seen with abruptio placentae (p less than 0.01). Sensitivity and specificity of CA 125 for abruptio placentae were 70% and 94%, respectively. Our data support a decidual source for CA 125 and may indicate utility of CA 125 as a marker for abruptio placentae.

Abruptio Placentae↗
PubMed1990

The neuropeptide histidyl proline diketopiperazine throughout human pregnancy: an inverse correlation with amniotic fluid prolactin.

Histidyl proline diketopiperazine values have been established in human amniotic fluid (n = 81) and maternal serum (n = 36) throughout gestation (10 to 42 weeks). Newborn cord serum (n = 10) and first-voided fetal urine (n = 10) levels were also documented. These measurements reveal increasing amniotic fluid levels with term gestation values (15,551 pg/ml) nearly thirteen-fold higher than maternal serum concentrations (1150 pg/ml). Corresponding fetal urine and cord serum concentrations were 16,781 and 2160 pg/ml, respectively. The amniotic fluid values are not influenced by fetal sex or maternal labor, nor do they correlate with amniotic fluid alpha-fetoprotein levels. However, there is a significant inverse correlation (r = -0.628; p less than 0.0001) between amniotic fluid prolactin and histidyl proline diketopiperazine after midgestation. The hypothesis that histidyl proline diketopiperazine may be a regulatory peptide for decidual prolactin production was tested by culturing term decidua in the presence of varying concentrations of histidyl proline diketopiperazine, but no inhibitory effect was observed. Decidual cultures did not produce measurable amounts of histidyl proline diketopiperazine. It is suggested that amniotic fluid histidyl proline diketopiperazine is derived from fetal urine.

Adolescent↗