[Lotus]

[Hi Diometres, 

Great questions. In past research (posted in this thread) I've learned there's more progesterone in glandular tissue and more prolactin in fat tissue. True, progesterone can store fat, but it's also catabolic to fat. And this statement seems paradoxical to me but progesterone stimulates ketones in the liver while storing glycogen...say what?. See the study below. I'll have check on progesterone cream studies and get back to you. On the range of progesterone in PC, it can vary for sure. Smokey Mountain I believe is 21mg per pump. Remember, skin absorption and liver metabolism are two of the biggest target tissue for hormone synthesis. PC inhibits DHT on the skin and in the breasts...it's bioidentical to progesterone. It's recommended you change up the location of application to prevent dermal fatigue. Let me know if I missed something. Btw, I like how you format your program thread

" Progesterone stimulates deposition of body fat but had catabolic effects on protein metabolism. Provisional evidence is offered that the steroid may influence ketone body production by the liver as well. When these steroid actions are considered together, their most relevant expression appears to be the physiologic changes observed during normal pregnancy. " 

.......perfect. This tells (suggests) me an additional opportunity for progesterone in breasts. Progesterone stimulates fat deposition in breasts, but is catabolic of protein. Two things come to mind, increasing protein intake prior to progesterone application, and the other is having muscle depletion (isometrics) of breast tissue followed by cold therapy. 

Metabolic effects of progesterone.

Kalkhoff RK. Am J Obstet Gynecol. 1982.

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Abstract

Progesterone has important effects on carbohydrate, lipid and protein metabolism. This steroid induced hyperinsulinemia, possibly by direct action on pancreatic islets, while promoting glycogen storage in the liver. Paradoxically, it antagonizes the effects of insulin on glucose metabolism in adipose tissue and skeletal muscle. Progesterone stimulates deposition of body fat but has catabolic effects on protein metabolism. Provisional evidence is offered that the steroid may influence ketone body production by the liver as well. When these steroid actions are considered together, their most relevant expression appears to be the physiologic changes observed during normal pregnancy. 

PIP: 

Parenteral progesterone injections into different mammalian species induce hyperinsulinemia, pancreatic islet hypertrophy, and exaggerated insulin secretion in vitro in response to glucose. The primary effect of progesterone by itself on carbohydrate metabolism appears to be the diversion of glucose utilization away from muscle and fat to other tissues, and the promotion of more storage of glycogen in the liver. On lipid metabolism, the 1 effect of progesterone is to favor storage of depot fat in adipose and breast tissue and to partially reduce the hypertriglyceridemic action of estrogens. On protein metabolism, it has been suggested that progesterone may have a catabolic action in man, and that the basic effects may be a lowering of several plasma amino acids and an increased total urinary nitrogen excretion without an associated aminoaciduria. On ketone body metabolism, progesterone partially suppresses the estrogen effect on liver triglyceride formation while promoting ketogenesis. The metabolic effects of progesterone are most relevant to pregnancy. The hormonal milieu of early to midgestation favors the stimulation of hyperphagia, pancreatic islet hypertrophy, hyperinsulinemia, and body fat and glycogen deposition. This period promotes maternal tissue accretion and weight gain. During the later half of pregnancy, progesterone acts simultaneously with prolactin and other hormones to prepare the breasts for lactation by promoting hyperinsulinemia and fuel storage and by helping to condition the liver in elaborating ketones more promptly to meet the demands of advancing pregnancy.

Hi Steve, (and thanks).  

Here's something interesting, the study and (follow up study below) track prolactin production in human breasts tissue indicating adipose (fat tissue) creates more prolactin than glandular tissue. Prolactin in adipose is described as a circulating hormone. Note the 10 fold increase by day 10. So, progesterone lowers PRL and estradiol had no effect in this study.  

In other words, having more fat in your breasts would indicate a higher presence of prolactin, conversely, more glandular would indicate higher progesterone.....in theory (lol, just an opinion). Higher prolactin in men turns off the pituitary signal to make more T, and although estradiol is unaffected (in this study) one should believe it's keeping estradiol low.....aka- no boob growth. So if indeed prolactin is cyclic in nature, (peaks on day 10) the other nine days are optimal growth cycles for breasts......feel free to chime in. 

Prolactin expression and secretion by human breast glandular and adipose tissue explants.

Zinger M1, McFarland M, Ben-Jonathan N.

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Abstract

Prolactin (PRL) is a 23-kDa hormone produced by the pituitary and extrapituitary sites. The main target of PRL is the breast, where it affects cellular growth, differentiation, and milk production. Recent evidence suggests that locally produced PRL plays a role in breast tumorigenesis. Our objective was to examine PRL synthesis/release in different tissues of the human breast and determine the effect of ovarian steroids. Breast tissue, obtained from women undergoing mastectomy or breast reduction, was separated into glandular (nonmalignant) and adipose explants and incubated for 10 d. Conditioned media were analyzed for PRL by a bioassay. PRL release from glandular explants decreased by 60% from d 1-3, followed by a 4-fold increase on d 10. PRL release from adipose explants was unchanged from d 1-3 and increased more than 10-fold by d 10. PRL gene expression, determined by RT-PCR, was low on d 0 and markedly increased on d 10 in both types of explants. De novo synthesis of PRL was confirmed by metabolic labeling. Progesterone suppressed PRL release from glandular explants without affecting adipose explants. Estradiol did not alter PRL release from either tissue. In conclusion, the human breast produces and releases bioactive PRL, with a higher release rate by adipose than glandular tissue. The time-dependent rise in PRL release suggests removal from inhibitory control. Progesterone may be one of the factors that suppresses PRL production in the glandular compartment, whereas the factor(s) that regulate adipose PRL are unknown. These data suggest an autocrine/paracrine role for PRL in human glandular and adipose breast tissue. 

Adv Exp Med Biol. 2015;846:1-35. doi: 10.1007/978-3-319-12114-7_1.

Prolactin (PRL) in adipose tissue: regulation and functions.

Ben-Jonathan N1, Hugo E.

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Abstract

New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affects adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance. 

PMID: 25472532  DOI: 10.1007/978-3-319-12114-7_1

Progestogens and venous thromboembolism in menopausal women: an updated oral versus transdermal estrogen meta-analysis

P-Y Scarabin. Climacteric. 2018 Aug.

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Abstract

Postmenopausal hormone therapy (HT) is a modifiable risk factor for venous thromboembolism (VTE). While the route of estrogen administration is now well recognized as an important determinant of VTE risk, there is also increasing evidence that progestogens may modulate the estrogen-related VTE risk. This review updates previous meta-analyses of VTE risk in HT users, focusing on the route of estrogen administration, hormonal regimen and progestogen type. Among women using estrogen-only preparations, oral but not transdermal preparations increased VTE risk (relative risk (RR) 1.48, 95% confidence interval (CI) 1.39-1.58; RR 0.97, 95% CI 0.87-1.09, respectively). In women using opposed estrogen, results were highly heterogeneous due to important differences between the molecules of progestogen. In transdermal estrogen users, there was no change in VTE risk in women using micronized progesterone (RR 0.93, 95% CI 0.65-1.33), whereas norpregnane derivatives were associated with increased VTE risk (RR 2.42, 95% CI 1.84-3.18). Among women using opposed oral estrogen, there was higher VTE risk in women using medroxyprogesterone acetate (RR 2.77, 95% CI 2.33-3.30) than in those using other progestins. These clinical findings, together with consistent biological data, emphasize the safety advantage of transdermal estrogen combined with progesterone and support the current evidence-based recommendations on HT, especially in women at high VTE risk.

Transdermal E2 is effective at enlarging breasts and increasing feminizing subcutaneous fat, increasing sex hormone-binding globulin (although less than oral E/E2) and thus, decreasing free (active) T. However, transdermal E2 carries less increased risk for venous thromboembolism (VTE)

https://academic.oup.com/jcem/article/10...81/5270376