To study the bioequivalence of a kind of progesterone sustained release suppository, a randomized cross-over study was conducted in 12 rabbits. A single rectal dose of 2.75 mg/kg progesterone sustained released suppository (tested formulation, T) and progesterone suppository (reference formulation, R) was administered; a multiple dose of 2.75 mg/kg was given up to seven times with an interval of 8 h. Concentrations in serum were determined by a competitive enzyme immunoassay. The main parameters of T were: for single and multiple doses, Cmax was 48.8 +/- 11.8 ng/mL and 43.5 +/- 9.4 ng/mL, Tmax was 0.5 +/- 0.3 h and 0.4 +/- 0.3 h, AUC(0-24 h) was 362.4 +/- 143 ng x h x mL(-1) and 310.6 +/- 70.3 ng x h x mL(-1), respectively. The relative bioavailability of T to R were (104.2 +/- 13.4)% and (111.4 +/- 19.1)%, respectively. Statistical analysis showed that the two formulations were bioequivalent and T had sustained released feature.
Administration, Rectal ; Biological Availability ; Cross-Over Studies ; Progesterone/administration & dosage ; Progesterone/*pharmacokinetics ; Random Allocation ; Suppositories

To investigate the effects of the property of drugs and the structure of drug delivery devices on the drug release rate, the effects of sealing methods, length, thickness and drug-loading manner of the silicone tubes on the drug release rate were examined using progestin, testosterone, estradiol as the delivery drugs. The results showed that the property of the drug was the crucial factor to the drug release rate. The sealing methods, length, thickness and drug status of the silicone tubes had significant effects on the drug release rate and the effects were closely related to the property of the drugs. In addition, our newly developed glass-silicone tube has larger drug deposition capability and smaller drug release area, offers an effective and convenient method for the sustained drug delivery with quick release traits in vivo.
Delayed-Action Preparations ; chemistry ; Drug Carriers ; administration & dosage ; chemistry ; Drug Delivery Systems ; Estradiol ; administration & dosage ; Progesterone Congeners ; administration & dosage ; Silicones ; Testosterone ; administration & dosage

BACKGROUNDFew studies have given suggestions on appropriate individual progesterone dosage in patients with progesterone deficiency. This study was designed to provide a reference for the clinical use of oral progesterone by exploring the relationship among Body Mass Index (BMI), dosage of progesterone, and serum progesterone concentration. Many gynecology and obstetrics doctors are unfamiliar with progesterone treatment. Our study is intended to help determine the dosage of oral progesterone.

METHODSThis was a block randomized, open-label, prospective clinical trial. Eighty women undergoing cessation of menses were recruited, given oral progesterone therapy for 10 consecutive days. They were randomly assigned to four groups (four different doses of progesterone, n = 20): group A 100 mg/d, group B 200 mg/d, group C 300 mg/d, and group D 400 mg/d.

RESULTSSeventy-four patients (92.5%, 74/80) completed the study. It was observed that administration of progesterone significantly increased serum progesterone concentration in the four groups (all P < 0.001). And there is a positive correlation between the increase and dosage (r(p) = 0.613, P < 0.001). A further linear regression analysis found the major regression equation: when 18.5 kg/m(2) ≤ BMI < 24 kg/m(2), Y = 8.4820×10(0.003X) (R(2) = 0.425, P < 0.001); Y was the increase of serum progesterone concentration in nmol/L, and X was the dosage of oral progesterone in mg/d.

CONCLUSIONSSerum progesterone levels went up linearly as the dosage increased. The higher the patient's BMI, the higher dosage would be needed to achieve the same serum progesterone concentration. The appropriate dosage of oral progesterone for different patients can be roughly calculated in light of the results of this study.

Administration, Oral ; Adult ; Body Mass Index ; Female ; Humans ; Menstruation Disturbances ; drug therapy ; Progesterone ; administration & dosage ; therapeutic use

Estrogen deficiency is the one of pathogenetic causes of postmenopausal osteoporosis. Exogenous estrogen may prevent postmenopausal bone loss, so to prevent postmenopausal osteoporosis and osteoporotic fracture. The effect of estrogen on postmenopausal syndrome can not be substituted with other medicine. However, the attention should be paid to the safety of hormone replacement therapy (HRT) during its long term use, and HRT should be used individually.
Aged ; Drug Therapy, Combination ; Estrogen Replacement Therapy ; Estrogens, Conjugated (USP) ; administration & dosage ; Female ; Humans ; Medroxyprogesterone ; administration & dosage ; Middle Aged ; Osteoporosis, Postmenopausal ; prevention & control ; Progesterone Congeners ; administration & dosage

OBJECTIVETo investigate the effects of oral dydrogesterone for luteal phase support after frozen embryo transfer (FET) cycles on the clinical outcomes.

METHODSA total of 1643 FET cycles in our center between January, 2010 and September, 2011 were analyzed. The patients were divided into group A with natural-cycle FET and group B with hormone replacement cycle (HRT-FET). The two groups were further divided into two subgroups to receive oral dydrogesterone (groups AI and BI, n=358 and 185, respectively) or intramuscular progesterone with progynova (groups AII and BII, n=634 and 466, respectively) as luteal phase support. The clinical pregnancy rates, implantation rates, early miscarriage rates, ectopic pregnancy rates, ongoing pregnancy rates and delivery rates were compared between the subgroups.

RESULTSThere were no significant differences in the clinical outcomes between the patients receiving dydrogesterone and intramuscular progesterone as luteal phase support in either natural-cycle FET or HRT FET (P>0.05).

CONCLUSIONIn the FET cycles, oral dydrogesterone tablets for luteal support can achieve good clinical outcomes comparable with those by intramuscular progesterone and serves as a good alternative for luteal phase support.

Administration, Oral ; Adult ; Dydrogesterone ; administration & dosage ; pharmacology ; Embryo Transfer ; methods ; Female ; Humans ; Middle Aged ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Progesterone ; administration & dosage ; pharmacology

The objective of this study was to investigate factors that influence the success of resynchronization protocols for bovines with and without progesterone supplementation. Cow synchronized and not found pregnant were randomly assigned to two resynchronization protocols: ovsynch without progesterone (P4) supplementation (n = 66) or with exogenous P4 administered from Days 0 to 7 (n = 67). Progesterone levels were measured on Days 0 and 7 of these protocols as well as 4 and 5 days post-insemination. Progesterone supplementation raised the P4 levels on Day 7 (p < 0.05), but had no overall effect on resynchronization rates (RRs) or pregnancy per artificial insemination (P/AI). However, cows with Body Condition Score (BCS) > 3.5 had increased P/AI values while cows with BCS < 2.75 had decreased P/AI rates after P4 supplementation. Primiparous cows had higher P4 values on Day 7 than pluriparous animals (p = 0.04) and tended to have higher RRs (p = 0.06). Results of this study indicate that progesterone supplementation in resynchronization protocols has minimal effects on outcomes. Parity had an effect on the levels of circulating progesterone at initiation of the protocol, which in turn influenced the RR.
Animals ; Cattle/*physiology ; Dinoprost/administration & dosage/*pharmacology ; Estrus Synchronization/*drug effects/methods ; Female ; Fertility Agents/administration & dosage/pharmacology ; Gonadotropin-Releasing Hormone/administration & dosage/*pharmacology ; Insemination, Artificial/veterinary ; Ovulation/drug effects ; Pregnancy ; Progesterone/administration & dosage/*pharmacology ; Tromethamine/administration & dosage/*pharmacology

Telomeres undergo attrition with each cell division, and telomere length is associated with age-related diseases and mortality in the elderly. Estrogen can influence the attrition of telomeres by diverse mechanisms. This is a retrospective case control study that investigated the influence of long-term hormone therapy (HT) on telomere length in postmenopausal women. We recruited 130 postmenopausal women from 55 to 69 years of age for this study, and divided them into two groups. The first group included 65 women who had been on estrogen and progesterone therapy for more than five years (HT group). The other group was composed of 65 women matched in age to the HT group who had never had HT (non- HT group). The relative ratios of telomere length of study subjects to a reference DNA from a healthy young female were measured using quantitative PCR. Plasma levels of lipid profiles, total antioxidant status (TAS), C-reactive proteins (CRP), fasting glucose levels, and estradiol levels were measured. Age at menopause, vitamin use, and exercise, alcohol, and cigarette smoking histories were also assessed in a questionnaire. Mean duration (+/- SD) of HT was 8.4 +/- 2.3 years. Prevalence of vitamin use and regular exercise were higher in the HT group than in the non-HT group (p < 0.01). Relative telomere length ratios in the HT group were significantly greater than those in the non-HT group (p < 0.01). HT was significantly correlated with the relative telomere length ratio in multivariate analysis when potential confounding variables were controlled for (p < 0.05). In conclusion, telomere lengths were longer in postmenopausal women who had a history of long-term HT than in postmenopausal women without HT. Long-term HT in postmenopausal women may alleviate telomere attrition.
Aged ; DNA Damage ; Estrogens/*administration & dosage ; Female ; *Hormone Replacement Therapy ; Humans ; Middle Aged ; Postmenopause ; Progesterone/*administration & dosage ; Research Support, Non-U.S. Gov't ; Telomere/*drug effects ; Time Factors

OBJECTIVETo observe the effects of long-term and low-dose hormone replacement therapy on bone mineral density (BMD), and the incidence of bone pain in postmenopausal women.

METHODSTotally 141 postmenopausal women were selected from the medical staff of the Peking Union Medical College Hospital. Of them, 63 women treated with low-dose sex hormone for over 5 (5-32) years were divided into hormone replacement therapy (HRT) group, and 78 never receiving HRT were divided into control group. The BMD was measured by dual energy X-ray absorptiometry (DEXA) at lumbar spine, Ward's triangle, femoral neck, trochanter, and total hip, and the incidence of bone pain was inquired.

RESULTSThe BMD in the HRT group was 9.1% higher than that in the control group (P < 0.05). The incidence of bone pain was significantly lower in the HRT group (71.4%) than that in the control group (89.7%).

CONCLUSIONLong-term and low-dose hormone replacement therapy can reduce bone loss and the incidence of bone pain.

Absorptiometry, Photon ; Bone Density ; Estrogens ; administration & dosage ; Female ; Hormone Replacement Therapy ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; prevention & control ; Progesterone ; administration & dosage

OBJECTIVETo establish a RP-HPLC method for determination of plasma progesterone and to apply the method for pharmacokinetics study of progesterone-loaded lipid nanoparticles after oral administration in rats.

METHODSThe plasma samples were collected from castrated rat after oral administration of progesterone-loaded lipid nanoparticles and extracted by acetic ether. The determination was performed on a Hypersil C18 column (150 mm X 3.9 mm , 5 microm) with a mobile phase consisting of methanol and water (60:40) at a flow-rate of 0.6 ml/min. The UV detector was at 240 nm and danazol was used as internal standard.

RESULTGood linearity was obtained over the range of 0.02-2 microg/ml progesterone in plasma(r=0.9999, n=3). The quantification limit was (0.02 +/-0.004) microg/ml(n=3) and the limit of detection was 0.005 microg.mL(-1)(S/N = or >3). The inter-and intra-day RSDs were all less than 10% for quality control samples at high-, medium- and low-concentrations. The average absolute recovery rate was 90.5 % and the average method recovery was in the range of 93.4 %-107.5%. The plasma concentration-time curves indicated that tmax was delayed after administration of progesterone-loaded lipid nanoparticles, and the bioavailability was increased significantly, compared with contrast solution.

CONCLUSIONThe method developed is stable, simple, rapid, accurate, sensitive and applicable for determining plasma concentrations of progesterone of progesterone-loaded lipid nanoparticles in pharmacokinetic studies.

Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; methods ; Drug Compounding ; Lipids ; chemistry ; Male ; Nanoparticles ; Progesterone ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

To compare an injectable progesterone (MAD-4) with an intravaginal device (IPD), and natural O17 with synthetic oestradiol (OB) in a synchronisation protocol, 51 cows were divided into four groups. Each group was treated with one of the two sources of progesterone and one of the two oestradiol formulations. Oestrus behaviour, follicle diameter, and pregnancy rates were evaluated. Oestrus behaviour (p = 0.902), numbers of cows in oestrus (p = 0.917), follicle diameter (p = 0.416), and pregnancy rates (p = 0.873) were similar among the four groups. More cows in the group treated with the IPD and OB scored > 200 oestrus behaviour points compared to the other groups (p = 0.038). A longer interval between the end of treatment and oestrus was observed among cows treated with MAD-4 than cows given the IPD (p = 0.030), but no differences were found between animals receiving the two oestradiol formulations (OB and O17). While the use of MAD-4 requires further testing, similar responses to natural oestradiol observed in the present study could allow the use of this formulation in reproductive protocols because it is not associated with the potential human health risks of OB.
Administration, Intravaginal ; Animals ; Cattle ; Estradiol/administration & dosage/*analogs & derivatives/*pharmacology ; Estrus/drug effects ; Estrus Synchronization/*methods ; Female ; Injections, Subcutaneous/veterinary ; Ovarian Follicle/drug effects ; Postpartum Period/drug effects ; Pregnancy ; Pregnancy Rate ; Progesterone/administration & dosage/*pharmacology ; Reproduction/drug effects