Progesterone

[Oriah]

weak androgen receptor agonists have an anti androgeic effect by binding to androgen receptors and causing less stimulation than endogenous androgens.

[KayXo]

weak androgen receptor agonists have an anti androgeic effect by binding to androgen receptors and causing less stimulation than endogenous androgens.

I agree but it would be better to have a progestin (or other substance) which binds the androgen receptor with no agonist activity at all, like bicalutamide, drospirenone, spironolactone or cyproterone acetate ALTHOUGH the 3 progestins mentioned also appeared to have agonist effects at the androgen receptor level in mice/rats (whether this can be applied to humans is questionable not only due to species but doses used). Also, the study you provided suggested, I think that norgestimate was more anti-androgenic than cypro. In the end, I would rather take something that occupies the androgen receptor with no agonist activity at all and drospirenone does appear superior. Bicalutamide is best.

Do you take birth control pills?

[Lara1969]

What do you think about Chlormadinone as anti androgenic progestine?

[KayXo]

Appears to be quite similar to Androcur in how it works but weaker in anti-androgenic properties. May have androgenic action (based on studies in rats and mice?).
We had an earlier discussion about this...
https://www.susans.org/forums/index.php/topic,158924.msg1352121.html#msg1352121

[Jamie D]

What do you think about Chlormadinone as anti androgenic progestine?

Chlormadinone - that is a new name to me.  And we have no wiki entry on it.

[Mirian]

So, after a few days on progesterone, I'm starting to feel really good, calm and stable (no stress) and my breasts are definitely more swollen, still sore, areola+nipple forming a mound (already!) on top of breasts, breasts more bouncy and tender, areolas darker and wider, breasts fuller. Libido is sometimes more intense than usual but nothing really out of the ordinary.

What I'm really hating though is the "high" that I get from it, 1-2 hours after taking it. I get really dizzy and I'm totally out of it. I don't feel this, of course, if I go to bed soon after taking it. I take P twice daily due to half-life. Always with food (and grapefruit, although effect is variable and may be only slight) to increase absorption. Food doubles concentration. In any case, the effect only lasts about 30-40 mins now and I'm thinking I will probably get used to it eventually. So, I'm ready to bite the bullet for a little while more.

Thank you as ever for the update. Nice to read you feel better and calmer and unstressed. And that
your breast is on ! Unfortunately I can't tell the same about mood, I'm to the point of literally quarreling
with people, I feel angry and impatient about everything, and then I cry. Quite typical of lack of P,
but as you know, I still have before to test increasing E. This is my first day with 3 Estreva pumps,
let's wait and see... surely, if I notice my feelings worsening with 3 pumps, and then even worsening
with 4, I'll be quite sure enough I simply need P. Some people uses to say what I experience is also
what most menopausal women do. But that could even simply due to lack of E indeed.
There could still be a third chance after all... that I might actually need both things: more E anyway, and
ALSO P.

[KayXo]

I'm to the point of literally quarreling with people, I feel angry and impatient about everything, and then I cry.

Usually, such symptoms are from lack of E BUT I've had those persist (even worsen?) with higher doses of E. Could be that I was still not taking enough, but that wouldn't make sense considering breast growth started on higher doses and was quite significant. Usually the threshold for well-being is lower (or equal) than for breast growth. Since adding P, I'm no longer tense or hyper. Very serene indeed. So, for me, P was the missing ingredient! At least, so far.   

[KayXo]

Volume 18a of Elsevier's New Comprehensive
Biochemistry, Titled 'Hormones and Their Actions, Part I', editors BA
Cooke, RJB King and HJ van der Molen.  Published 1988.  ISBN
0-444-80996-1.  Dewey 612.405.

Chapter 14: Progesterone action and receptors, by
Nancy L Krett, Dean P Edwards and Kathryn B Horwitz, of the University
of Colorado Health Sciences Centre, Denver.

"Progesterone also acts synergistically with estrogen in the normal
development of the breast.  Estrogen stimulates cell mitosis and growth
of the ductal system, while lobular development and differentiation is
dependent on progesterone.  When estrogen is administered in the absence
of progesterone, the tubular system proliferates and the ducts dilate
resulting in the formation of cysts and fibroses.  These changes are
comparable to those observed in fibrocystic disease and are suppressed
by progestins, so that normal breast development requires that estrogen
and progesterone be administered together.[2-4]"

References:
2.  Ross GT (1985) In: Textbook of Endocrinology (Wilson JD and Foster
DW, eds) pp 206-258.  WB Saunders, Pennsylvania.
3.  Mauvais-Jarvis P, Kutten F and Gompel A (1986)  Ann. N.Y. Acad. Sci.
464, 152-167.
4.  Mauvais-Jarvis P, Kutten F and Gompel A (1986)  Breast Cancer Res.
Treat. 8, 179-187.

[kira21 ♡♡♡]

Can I bring up the subject of progesterone and oestrogen receptors. The number of receptors seems to be influenced by the presence of these hormones.

This document about oestrogen increasing progesterone sensitivity is interesting:
REGULATION OF PROGESTERONE RECEPTOR FORMATION BY ESTROGEN ACTION*

Wendell W. Leavitt2, Tong J. Chen2, Thomas C. Allen2, J. O'Neal Johnston1
Article first published online: 16 DEC 2006

http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1977.tb29418.x/abstract

There are others that link oestrogen to increase in progesterone receptors. I have heard suggestions that progesterone increases sensitivity of oestrogen receptors, but I have yet to find good studies to support this.

I think there is a certain amount of interesting discussion to be had about regimens should this be the case.

[KayXo]

Volume 18a of Elsevier's New Comprehensive
Biochemistry, Titled 'Hormones and Their Actions, Part I', editors BA
Cooke, RJB King and HJ van der Molen.  Published 1988.  ISBN
0-444-80996-1.  Dewey 612.405

Chapter 14: Progesterone action and receptors, by
Nancy L Krett, Dean P Edwards and Kathryn B Horwitz, of the University
of Colorado Health Sciences Centre, Denver.

"Depending on the physiological state, progesterone may antagonise
estrogen action.  One effect of estradiol is to increase the levels of
progesterone receptors (PR).  Binding of progesterone to its receptors
then leads not only to progestational effects, but also antiestrogenic
effects by causing a reduction in estrogen secretion into the systemic
circulation; by stimulating the enzyme 17B-hydroxysteroid dehydrogenase
which converts estradiol to the less active estrogen estrone; and by
lowering the levels of estrogen receptors in cells thereby decreasing
the ability of target tissue to respond to estradiol [4].

CLIMACTERIC 2005;8(Suppl 1):3–63
Pharmacology of estrogens and progestogens: influence of different routes of administration

"In the breast of primates, progestogens may reduce the expression of the ERa and PR, but the estrogen-induced proliferation of the mammary epithelium is not inhibited, but enhanced by progestogens203."

"In contrast to the endometrium, progesterone and most synthetic progestins enhance the proliferative
effect of estrogens on breast epithelium."

"The primary role of progestogens in HRT is the inhibition of estrogen-induced proliferation of the
endometrium. Moreover, they induce secretory changes in a proliferated endometrium. The
antiestrogenic effect of progestogens in the endometrium is associated with a suppression of ER
and the activation of the 17b-HSD type 2 which converts estradiol to estrone, and the estronesulfotransferase which causes conjugation of estrone."

"Besides their effect on the endometrium, synthetic progestins may act on the vaginal
epithelium as antiestrogens and reduce the maturation index. In the cervix, they reduce the
amount and spinnbarkeit of the mucus, in the tubes they control motility and composition of
fluid, and in the breast they enhance estrogen induced proliferation of mammary epithelium.
Except dydrogesterone, the progestogens may influence central nervous system function and
psyche, inhibit gonadotropin release, increase body temperature, and antagonize various central
effects of estrogens."

"Due to their antiestrogenic effect, progestogens, including progesterone, may counteract the stimulatory and excitatory effects of estrogens on the brain. Beyond this, progesterone exerts a pronounced sedative effect after conversion to 5alpha and 5b-pregnanolone, which bind to the GABAA-receptor. The receptor binding affinity and hormonal activity of metabolites of some synthetic progestins have been investigated (Table 11). It is known that 3a-hydroxy-CMA and 15b hydroxy-CPA exert a pronounced antiandrogenic effect. Some reduced metabolites of the nortestosterone derivatives show some antiandrogenic or androgenic effects, or even a slight estrogenic"

"Owing to their antiestrogenic properties, progestogens may antagonize the stimulatory effects on the central nervous system of estrogens. They may reduce the number of ERs and of synaptic connections, attenuate the effect of excitatory amino acids, and increase the inactivation of neurotransmitters. This may explain the unfavorable effect of progestogens on mood of predisposed women, e.g. in women with a history of premenstrual syndrome320. It has been shown that MPA may impair the beneficial effects of CEE on depressive mood and other psychological symptoms in postmenopausal women 321. The mutual interactions between estrogens and progestogens are still controversially discussed"

[KayXo]

From http://www.endotext.org/male/male14/male14.htm

"Estrogen and progesterone act in an integrative fashion to stimulate
normal adult female breast development. Estrogen, acting through its
ER a receptor, promotes duct growth, while progesterone, also acting
through its receptor (PR), supports alveolar development (15). This
is demonstrated by experiments in ER a knockout mice which display
grossly impaired ductal development, whereas the PR knockout mice
possess significant ductal development, but lack alveolar
differentiation (28,6)."

"In addition, clinical studies have correlated maximal cell
proliferation to specific phases in the female menstrual cycle. For
example, maximal proliferation occurs not during the follicular phase
when estrogens reach peak levels and progesterone is low (less than 1
ng/mL [3.1nmol}), but rather, it occurs during the luteal phase when
progesterone reaches levels of 10-20 ng/mL (31- 62nmol) and estrogen
levels are two to three times lower than in the follicular phase
(42)."

"Given these data and the fact that PR knockout mice lack alveolar
development in breast tissue, it appears as if progesterone,
analogous to estrogen, may increase GH secretion and act through its
receptor on mammary tissue to enhance breast development,
specifically alveolar differentiation (28, 18)."

GH= growth hormone
ER= estrogen receptor
PR= progesterone receptor

[kira21 ♡♡♡]

That's very interesting. I don't suppose that you have the references from that excerpt do you? You need an account to read from the link that you sent and I don't have one.

Thanks!

Akira

[KayXo]

You can register for free. That's what I did!

[kira21 ♡♡♡]

I did! Thanks :-)

[KayXo]

Well, all I gotta say after one week on P is that ...

E+P better than E alone. Wow! Definite synergistic effect. Work beautifully well together. Just surrender to the power of E and P and you shall fly higher than you ever imagined...

[amZo]

Well, all I gotta say after one week on P is that ...

E+P better than E alone. Wow! Definite synergistic effect. Work beautifully well together. Just surrender to the power of E and P and you shall fly higher than you ever imagined...

Works wonders for the hips and rear end too...

[Jill F]

I find that after about the first week, P can get a bit cloying.  I was glad to get off of that ride today.  The P cycle also seemed mellower this round than last time.  Maybe I'm acclimating?

[KayXo]

Works wonders for the hips and rear end too...

Perfect! Can't wait! 

[Gina_Z]

This posted by KayXo worries me about the benefits of progesterone:
!!!!!

"Depending on the physiological state, progesterone may antagonise
estrogen action.  One effect of estradiol is to increase the levels of
progesterone receptors (PR).  Binding of progesterone to its receptors
then leads not only to progestational effects, but also antiestrogenic
effects by causing a reduction in estrogen secretion into the systemic
circulation; by stimulating the enzyme 17B-hydroxysteroid dehydrogenase
which converts estradiol to the less active estrogen estrone; and by
lowering the levels of estrogen receptors in cells thereby decreasing
the ability of target tissue to respond to estradiol [4].

[Lara1969]

Therefor a cyclical progesterone intake is maybe the best solution.