Related Experiment Videos
[Effects of o,p'-DDD on pituitary-gonadal function in patients with Cushing's disease]
1Third Department of Internal Medicine, Fukushima Medical College, Japan.
Abstract:
O,p'-DDD has a cytotoxic action and inhibits the cholesterol side chain cleavage enzyme, 11 beta-hydroxylase, 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase and 21-hydroxylase of the adrenal cells. However, the effects of o,p'-DDD on gonadal steroidogenesis are still unknown. In the present study, the effects of o,p'-DDD on Plasma cortisol, pregnenolone, 17 alpha-hydroxypregnenolone (17-OH-pregnenolone), progesterone, 17 alpha-hydroxyprogesterone (17-OH-progesterone), 11-deoxycorticosterone (DOC), corticosterone, dehydroepiandrosterone (DHEA), delta 4-androstenedione (androstenedione), estradiol, and LH and FSH were investigated in 3 patients with Cushing's disease before and after the administration of o,p'-DDD. The results are presented here. In Case 1 (18 yr old female) who had had secondary amenorrhea for 2 years, the plasma levels of cortisol, pregnenolone, 17-OH-pregnenolone, DHEA, androstenedione, testosterone, estradiol and corticosterone were elevated. The basal levels of plasma LH and FSH and the responses of both gonadotropins were lower than those of women with eumenorrhea. The plasma levels of progesterone, DHEA and testosterone decreased to normal 2 months after the beginning of the administration of o,p'-DDD. She restored menstrual cycles ranging from 40 to 50 days 3 months after the administration of o,p'-DDD, but with anovulatory bleeding. She showed a biphasic body temperature pattern with plasma progesterone and estradiol levels indicating corpus luteum formation 11 months after the start of the treatment, when plasma cortisol as well as progesterone and androgen were reduced to normal. The basal levels of FSH and LH and responses of these gonadotropins were slightly improved at that time. The plasma levels of cortisol, DHEA and androstenedione were high in Case 2 (38 yr old male) and Case 3 (45 yr old male), whereas plasma testosterone level was normal in Case 2 and low in Case 3. The plasma levels of these 3 steroids were normalized 28 days after the beginning of the o,p'-DDD administration. These results suggest that o,p'-DDD does not interfere with gonadal steroidogenesis in Cushing's disease.
Insights
O,p-DDD treatment normalized hormone levels in Cushing's disease patients. This suggests o,p-DDD does not interfere with gonadal steroidogenesis, potentially aiding reproductive function restoration.
Area of Science:
- Endocrinology
- Reproductive Biology
- Oncology
Background:
- O,p'-DDD is known to inhibit adrenal steroidogenesis by affecting key enzymes.
- The impact of o,p'-DDD on gonadal steroidogenesis remains largely uncharacterized.
- Cushing's disease involves adrenal hypercortisolism, often with associated hormonal imbalances.
Observation:
- This study investigated o,p'-DDD's effects on plasma hormone levels in three Cushing's disease patients.
- Measurements included cortisol, pregnenolone, progesterone, androgens, estrogens, and gonadotropins (LH, FSH).
- Hormonal profiles were assessed before and after o,p'-DDD administration.
Findings:
- In a female patient with secondary amenorrhea, o,p'-DDD normalized elevated progesterone, dehydroepiandrosterone (DHEA), and testosterone levels.
- Menstrual cycles and signs of corpus luteum formation were restored, with normalized estradiol and progesterone.
- In two male patients, o,p'-DDD normalized elevated cortisol, DHEA, and androstenedione levels within 28 days.
Implications:
- These findings suggest o,p'-DDD does not adversely affect gonadal steroidogenesis in Cushing's disease patients.
- The drug may contribute to restoring reproductive function and hormonal balance in affected individuals.
- Further research is warranted to confirm these effects and explore therapeutic potential.